Evaluating regression of morbidity associated with parasitic infections is an important component of community-based control programmes. We performed an intervention against Schistosoma mansoni infection, focusing on hepatosplenomegaly in the absence of periportal fibrosis, in a cohort of 67 Kenyan children aged 7-18 years from Makueni District, selected on the basis of hepatosplenomegaly detected by ultrasonography. Clinical and ultrasound examinations were conducted annually for three years after treatment, and the source of infection (a river) was regularly treated with molluscicide, thereby severely reducing exposure to schistosomiasis. Malaria transmission was uninterrupted. The prevalence of hard spleens, and the magnitude of clinically assessed splenomegaly along the mid-axillary and mid-clavicular lines decreased monotonically over time, independently of age, whereas clinically measured hepatomegaly along the mid-sternal line and the prevalence of firm livers decreased in an age-specific manner, being more pronounced amongst children aged 14 years or older at enrolment. Ultrasound data were less informative, and did not concur with clinical observations. These results demonstrate that praziquantel treatment reduces hepatosplenomegaly in the absence of exposure to S. mansoni, even with continuing exposure to malaria. The lack of complete resolution of hepatosplenomegaly in most children suggests, among other things, a residual organomegaly attributable to malaria.