To determine the effect of targeted field administration of oral chemotherapeutic agents on the prevalence, intensity, and morbidity of Schistosoma haematobium infections, we initiated a long-term school-based program in the Msambweni area of Kwale District, Coast Province, Kenya. Prior to treatment, 69% of the children examined (ages 4-21, n = 2,628) were infected; 34% had moderate or heavy infections (> 100 eggs/10 ml urine). Infected individuals were randomized to receive, during one year, either metrifonate (10 mg/kg × 3 doses) or praziquantel, (40 mg/kg × 1 dose). At the end of the first year, prevalence of infection fell to 19%; only 2% of the pupils remained in the moderately and heavily infected groups. Corresponding decreases in the prevalence of hematuria (54% in 1984 vs. 16% in 1985) and proteinuria (56% in 1984 vs. 26% in 1985) were noted. These were associated with significant declines in bladder thickening and irregularities noted during ultrasound examinations, but not with decreases in hydronephrosis. There was no significant difference in the post-treatment prevalence or intensity of infection after treatment with metrifonate as compared with praziquantel. These results demonstrate that field-applied chemotherapy with either agent offers a practical strategy for the control of S. haematobium infection and its associated morbidity.