Eighteen patients with Plasmodium vivax malaria were prospectively evaluated to assess the time of onset and extent of upper gastrointestinal mucosal injury caused by oral administration of four tablets (600-mg base) of chloroquine. Endoscopy was performed in the group of three separate patients. Each patient underwent endoscopy, both before the drug was given, and at intervals of 1, 2, 4, 12, 24, and 36 h. Before the drug was given, endoscopy was normal in all of the patients. However, mucosal erosions developed in four of 18 patients who were endoscoped 24 and 36 h after chloroquine ingestion (gastric, four; duodenal, two; esophageal, one). The same doses of chloroquine failed to produce any mucosal lesions when given to these four patients while they were afebrile and when given to 11 healthy individuals who served as controls. Poor correlation was noted between subjective symptoms and endoscopic findings. In conclusion, neither malaria alone nor chloroquine alone causes mucosal lesions. However, chloroquine administered during malarial fever causes mucosal damage in susceptible individuals.