Schistosoma haematobium is refractory to praziquantel (PZQ) during the prepatent period of infection. A hypothesis based on this observation is that in areas where S. haematobium transmission is seasonal, the outcome of chemotherapy depends on the timing of the treatment relative to the annual transmission pattern. To examine this hypothesis, a study was carried out in southern Mozambique. Following demonstration of seasonal transmission, PZQ was administered separately to two cohorts of S. haematobium-infected schoolchildren in (1) the high and (2) the low transmission seasons and followed up after two months when levels of infection and intensities were measured. The prevalence of infection decreased from 54·2% and 51·7% in cohorts 1 and 2 to 30·3% and 1·8%, respectively. The geometric mean intensity of infection decreased from 23·3 eggs/10 ml of urine at baseline to 15·6 eggs/10 ml of urine in cohort 1 (treated during high transmission season), and from 23·5 eggs/10 ml urine to 7·3 eggs/10 ml of urine in cohort 2 (treated during low transmission season). The observed cure rates in cohorts 1 and 2 were 69·7% and 98·2%, respectively. Differences in infection between the cohorts in terms of cure rate and level of infection two months post-treatment were statistically significant and indicate that in areas with a seasonal transmission pattern, the effect of PZQ can be enhanced if treatment takes place during the low transmission season. We conclude that appropriately timed PZQ administration will increase the impact of schistosomiasis control programmes.