Surprisingly low cure rates were repeatedly observed after treatment with a standard dosage of praziquantel in a recently established Schistosoma mansoni focus in northern Senegal. In 4 discrete cohorts from the same population, cure rates were 18-36% and egg count reduction rates were 77-88%. Data and material of 920 compliant subjects from all 4 cohorts were further analyzed to identify possible host-related factors associated with low cure rates. The lowest cure rates were found in the highest egg count groups. However, in low and moderate egg count groups, drug efficacy was also below normal values. Cure rates were similar in males and females, showed no seasonal variation, and were independent of previous praziquantel treatment. They were significantly higher in adults than in children, also after allowing for intensity of infection. Individual water contact behavior and specific humoral immune responses were examined in 2 extreme subgroups, either without significant egg count reduction or showing complete parasitologic cure. There was no significant difference in frequency and duration of water contact between those individuals with complete cure and those that showed little effect of praziquantel treatment. Levels of IgG, IgG1, IgG3, IgG4, IgM, and IgE against adult worm antigen were not different between the 2 subgroups. Thus, the abnormally frequent failure of treatment observed in this focus could not be associated with any host-related factor, other than age and pretreatment egg counts.