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Praziquantel is a newly developed drug effective in the treatment of schistosomiasis. In order to assess the efficacy and toxicity of praziquantel in the treatment of Schistosoma mekongi, 11 infected Laotian refugees, all belonging to a single extended family, were treated in a double-blind crossover trial with praziquantel and placebo. Initially, one group of five received praziquantel 60 mg/kg body weight in three divided doses orally while the remainder received an identically appearing placebo. Patients were evaluated clinically before, during and following therapy for 2 days. After 2.5 months the patients were re-evaluated and subjected to the opposite treatment, and final follow-up took place 5–7 months later. Three other patients were treated using an open protocol. All but one person was cured (91%). This patient failed to show a decrease in egg excretion 2.5 weeks after praziquantel therapy and was lost to follow-up thereafter. Side effects were common and consisted primarily of abdominal pain, malaise, and fever. These were generally mild and transient. No abnormal laboratory findings were associated with praziquantel therapy. At the final evaluation 6/6 patients with initial hepatomegaly showed a decrease in liver size.