Acute schistosomiasis (AS) is a systemic hypersensitivity reaction that has been recognized mostly in nonimmune travelers. Although the condition is self-limited, it can be severe. We describe an outbreak of AS in a group of travelers returning from Tanzania and estimate the disease burden. After we identified the index case, we initiated an epidemiological investigation of the entire group. Diagnosis was established on the basis of symptoms, serologic data, and ova detection. Relevant clinical information was documented with use of a structured questionnaire, and the patient's economic burden was recorded. Health-related quality of life was assessed during the illness and 3 months later. Of 34 group members, 27 had a single exposure to a fresh water pond, 22 (81%) of whom were infected. AS developed in 19 (86%) of the 22 infected travelers. Cough (78% of patients), fever (68%), and fatigue (58%) were the most common symptoms, with mean durations (+/- standard deviation) of 22 +/- 11, 11 +/- 7, and 37 +/- 16 days, respectively. The total number of medical encounters was 258 (mean no. of encounters per patient, 11), and 152 work and school days were missed (mean, 8 days per patient). During the acute phase of illness, there was a significant decline in health-related quality of life that returned to expected norms after 3 months. A single, short exposure of travelers to an infected pond led to a high infection rate. The illness had a significant impact on the patients' daily functions, and patients extensively used medical resources. Education to avoid exposure to fresh water remains the most effective method of schistosomiasis prevention.