Ninety-eight Schistosoma mansoni-infected children from an endemic area in Sharkia Governorate, Egypt were evaluated by abdominal ultrasonography to determine liver and spleen sizes, grade of periportal fibrosis, and splenic vein diameter. Circulating antigen levels were measured using a double sandwich ELISA in which the sensitivity was 91.8% and specificity was > 99%, with no evidence of cross-reactivity with other parasites. No significant relationship was observed between antigen level and clinical stages of the disease as assessed by physical examination (P > 0.05). When ultrasound was used to stage disease, the mean antigen level was significantly higher among hepatosplenic cases than intestinal cases (P < 0.05). No difference in mean antigen levels were found between the splenic and hepatic cases. Furthermore, a direct correlation (P < 0.01) was observed between antigen level and disease severity as monitored by ultrasonography. Antigen level showed a positive correlation with the degree of periportal fibrosis (P < 0.05). Moreover, a significant increase in the percent of children who were antigen positive (> 80 ng/ml) was found in those with more severe periportal fibrosis (P < 0.001). The findings suggest that ultrasonography along with measurement of circulating antigen levels predict morbidity in schistosomiasis mansoni.