We report the 5-year impact (1996-2001) of repeated praziquantel chemotherapy on subclinical morbidity related to Schistosoma japonicum infection. We repeated stool examinations and hepatosplenic ultrasonography in a cohort of 120 individuals living on an island with endemic infection in Dongting Lake, China. Prevalence of schistosome infection fell by 43% and intensity (geometric mean eggs per gram) declined by 80% over the 5 years. However, transmission persisted at a dangerously high rate of 13% per year for re-infection or new infection in the cohort. The prevalence of left-lobe enlargement and dilated portal vein fell significantly (P 0.05). However, endpoint infection was even more strongly associated with left-lobe enlargement (57% versus 15%, P < 0.01). The proportions of subjects with improved parenchymal and periportal fibrosis were much higher than the proportions of subjects that progressed (P < 0.05). Reduction of prevalence and intensity of infection, and improvement of subclinical morbidity, were benefits of repeated treatments. Further research is needed to understand why some patients developed fibrosis despite substantial reductions in egg counts and to evaluate the functional importance of residual subclinical morbidity after chemotherapy-based control in the lake and marshland area of Chin