We examined the effect of parasitologic cure of S. mansoni infection on liver fibrosis in mice. Praziquantel, 250 mg/kg body weight, was administered orally to mice 8 weeks after infection with 50 S. mansoni cercariae. We assessed liver fibrosis by chemical measurement of collagen content as measured by the estimation of hydroxyproline and by histologic examination at the time of treatment, and at 10 and 20 weeks post-treatment, in comparison with the same measurements in untreated S. mansoni-infected mice and age-matched normal control mice. The extent of infection was monitored by liver egg counts. Compared to normal uninfected mice, mice with untreated S. mansoni infection showed steady accumulation of liver collagen at the 3 measurement periods, reaching an average level of 15-fold greater than that found in normal mice at 28 weeks after infection. Mice treated with praziquantel showed a prompt decrease in S. mansoni liver egg load with no viable eggs 10 weeks after treatment. Liver fibrosis was modestly diminished in treated mice compared to untreated controls 10 weeks after treatment; fibrosis was arrested and liver collagen content had diminished to normal levels by 20 weeks after treatment. No praziquantel toxicity was noted. The survival of treated mice was markedly greater than that of untreated infected animals. We conclude that parasitologic cure of murine S. mansoni infection is followed by arrest and eventual partial reversal of liver fibrosis under the conditions employed.