The efficacy of praziquantel started during the incubation period of schistosomiasis has not been studied. Eighteen tourists were infected by Schistosoma haematobium during summer 2003 after bathing once in the same cascade in Mali. We observed the efficacy of praziquantel given at different phases. They received praziquantel at the first consultation, from Days 10 to 15 after exposure in eight asymptomatic patients (Group 1), from Days 28 to 40 in 4 asymptomatic patients (Group 2), and from Days 20 to 39 in 6 patients with acute schistosomiasis (Group 3). All Group 1 patients developed acute schistosomiasis, compared with none of the Group 2 patients (P < 0.004). Among the 10 patients treated during the acute phase, clinical status deteriorated in four cases. Seventeen of the 18 patients developed chronic schistosomiasis. Early praziquantel treatment was thus less effective than later treatment in preventing acute schistosomiasis, while neither treatment effectively prevented chronic schistosomiasis.