The impact of repeated selective chemotherapy on prevalences and intensities of infection with Schistosoma mansoni was evaluated in Gihungwe Transversals 1 and 2 (initial prevalence 60%) and Buhandagaza/Kizina (initial prevalence 35%), two village clusters in Burundi. Surveys were carried out at months -6, -3, 0, 3, 6, 9, 12, 24, and 36, with reference to the first intervention; treatment with praziquantel (40 mg/kg) was given at months 0, 12, 24, and 36 to subjects showing parasite eggs on a single 28-mg Kato slide. A second slide was examined for monitoring purposes only. Over the pre-intervention period, the overall prevalences and intensities remained relatively stable, but important increases were observed in specific groups. The cure rate three months after the first treatment in those treated was 73% (Gihungwe) and 83% (Buhandagaza/Kizina), but the prevalence at the community level was reduced only by 50% and 46%, respectively. Fifty-six percent and 79%, respectively, of the remaining positive cases had not been treated, largely because they were (falsely) negative at the screening. Reinfection occurred mainly in Gihungwe and in younger age groups. One year after the second treatment, prevalences and intensities were further reduced in Gihungwe only; one year after the third treatment prevalences were not reduced further in either village group. The final prevalence of infection was approximately 25%, with infections with an intensity of over 100 eggs per gram of feces approximately 5%, in all four villages. Over 80% of the remaining cases had not been treated at the previous intervention; the sensitivity of the screening method appears to be a major determinant of the outcome of repeated selective treatment.