The party hears rumors of a plague that is ravaging a nearby seaport. No healing methods have been successful at treating its effects. Some say it may be the result of a magical curse while others suggest that it is a plague sent by the gods.
Obviously, the party probably will need to be lured into the city - possibly some of them have relatives there, or they are hired by someone to rescue family members from the city. (Otherwise, they might just as well stay away to avoid contracting it themselves!) As they approach, they encounter a few of the dying attempting to flee from the city. They have lost motor skills, they sweat profusely and are completely disoriented - hallucinating. As they die, the party's efforts to help them will be unsuccessful.
It is interesting to note that the farms just outside of the port city have been mostly untouched, with only a few young males that frequented the city having been afflicted.
In the town, the party will encounter more plague victims. Most seem to be from the seedier parts of town, but there are also a number of high-ranking officials and shopkeepers that have died. With the number of dead bodies piling up, there have been a number of problems such as giant rats and ghouls feeding on the dead along with the problems of burying them all. (These can be turned into mini-adventures.)
As the party investigates, they learn that the plague started within the last month. None of the clerics or healers have found a way to treat the dying. Plus, spells that raise the dead don't even bring them back. Priests are convinced that this is a sign, and that "The gods are punishing us."
One of the main links appears to be money: many victims are thieves, harlots, shopkeepers and city officials while the poorer people in the same areas (beggars, workers, etc.) have been largely untouched. If they pursue this, they will learn of a mage in the port that believes this is due to some cursed coins being passed around the city. (He's wrong, but it can lead to some rather interesting side adventures.)
While the records are a bit sketchy, the party will find that most of the early deaths occurred close to the docks, and have since spread throughout the rest of the city. The party will also discover that a few of the once popular taverns near the docks are fairly deserted. Many of the former patrons have been hit by the disease. If they check these places out, they will notice that one particularly rich-looking fellow frequents most of these places. He stops in, talks to a couple people briefly and then leaves. If watched carefully, he will be seen exchanging small pouches under the table with those people.
He's was once a thief, but is now a rich drug-dealer. If confronted by the party, he will try to bribe them to leave him alone. If searched and then pressed about the drugs, he will reveal that he received a new type of drug "Drax" from a ship that arrived about a month ago. It has been a big seller for him, but recently a number of his distributors in the city have fallen victim to the disease. Thus, he has been forced to leave his fancy dwelling and go back onto the street to do the dealings in person again. He's been having to lower his price, for it seems that the drug's demand has been dropping off. (This is because the customers are dying, but he doesn't realize this.) His greed and low wisdom prevent him from making any kind of connection.
If the party convinces him that the drug is causing the disease, he will be very upset and try to help them as best he can to avoid a certain death at the hands of the local officials and populace. (He is chaotic, but not evil.) He will turn over all the Drax he possesses and a fair amount of gold to the party. He will also provide them with the names of the ship and his contacts, but then he will attempt to slip out of town permanently.
The drug does tremendous damage to the brain producing a spectacular high and hallucinations in the process. Eventually the entire brain is destroyed preventing any type of healing or raising from working.
Note: If this adventure were placed in modern day, the characters would probably figure out the drug source very quickly. Staging it in a fantasy campaign creates many more "believable" dead ends for the investigation such as cursed coins or a god-sent plague. DM's should feel free to take advantage of this by possibly spinning off various mini-adventures before the true source is determined.