Chemotherapy with praziquantel is the cornerstone of schistosomiasis control. In view of recent concern about tolerance or resistance to praziquantel, monitoring its efficacy in different epidemiological settings is required. We report a study among 253 schoolchildren in an area highly endemic for Schistosoma mansoni in western Côte d'Ivoire. After examining four consecutive stool specimens from each child, the first praziquantel treatment at 60 mg/kg divided into two doses was administered. Four weeks later, stool specimens were again screened over 4 consecutive days and revealed a cure rate of 71.6% and an egg reduction rate of 79.9%. There was a significant association between cure rate and intensity of infection prior to treatment with highest cure rates observed in light infections (P < 0.01). Praziquantel, at a single dose of 40 mg/kg, was again administered 35 days after the first treatment. The overall cure and egg reduction rates increased considerably. The association between cure rate and intensity of infection prior to the second treatment was significant but less pronounced. Twenty-two children remained S. mansoni positive after the two chemotherapy campaigns, and interestingly, many of these were only identified after repeated stool examinations. We argue that pre-patent infections may account for some of these 'treatment failures'. However, further studies in other endemic settings are needed, with parasitological diagnoses having a high sensitivity.