Schistosomiasis, in contrast to alcoholic liver disease, leads to presinusoidal hepatic fibrosis, which determines the prognosis of the disease. Because conventional liver function tests and liver biopsy specimens provide little information about the dynamics of the fibrotic process, we measured the serum concentrations of procollagen type III N-propeptide and procollagen type I C-propeptide, believed to mainly reflect collagen synthesis, and procollagen type IV C-propeptide and collagen type VI, two presumptive markers of collagen degradation. Determinations were performed in 15 healthy control subjects, 69 patients with various stages of infection with Schistosoma mansoni/Schistosoma haematobium (28) with an early active infection and no organ involvement, 27 with hepatosplenic involvement and 14 with complications of portal hypertension) and 16 patients with alcoholic cirrhosis. In addition, liver biopsy specimens were obtained from 30 schistosomal patients (18 with hepatosplenic involvement and 12 with complications of portal hypertension for histopathological grading and collagen histochemistry. Procollagen type III N-propeptide was significantly elevated in the three patient groups with schistosomiasis when compared with controls (p < 0.01). Also, patients with higher histological grading showed significantly higher procollagen type III N-propeptide values (p < 0.05). In alcoholic patients, procollagen type III N-propeptide was even higher and increased parallel to the severity of the disease, determined by using a combined clinical and laboratory index. Procollagen type I C-propeptide was only elevated in early infection (p < 0.05) and steadily decreased with disease progression. In contrast, procollagen type IV C-propeptide and collagen type VI were not significantly elevated in those patients with no organ involvement but increased significantly in those patients with hepatosplenic involvement (p < 0.01) and those patients with complications of portal hypertension (p < 0.01 and p < 0.02, respectively). Immunohistological findings for the above mentioned collagen types did not correlate with their corresponding serum levels. The data show that a serum elevation of procollagen type III N-propeptide may indicate early fibrogenic activity in patients with schistosomal infection; in addition, the combined measurement of procollagen type III N-propeptide with procollagen type IV C-propeptide and collagen type VI seems to provide additional information to predict progressive hepatic fibrosis. (Hepatology 1992;15:637–644).