An antigen-capture ELISA using monoclonal antibody (MAb) 128C3/3/21 was used to detect circulating parasite-derived antigens in the sera of patients actively infected with Schistosoma haematobium (31 males and four females, 5-25 years of age). The assay had a sensitivity of 100% (35 of 35 patients with antigen levels > 80 ng/ml) and a specificity > 99%. We used this ELISA to monitor antigenemia before treatment and one, three, and six months after treatment with a single oral dose of praziquantel (PZQ) (60 mg/kg in 20 patients or 40 mg/kg in 15 patients) and compared our findings with those indicated by other measures of disease progression. Circulating antigen levels decreased drastically after PZQ treatment (P < 0.001), with a significantly higher decrease occurring after treatment with 60 mg/kg than with 40 mg/kg. Although the mean antigen level was still significantly reduced (P < 0.001) at six months after treatment, 16 patients remained antigen-positive after six months, and nine had increased levels of antigenemia, reflecting reinfection in six patients and persistence of infection in another. We observed a correlation (r = 0.6, P < 0.01) between the level of circulating antigen and the intensity of infection as measured by egg count. We also found a direct relationship (P < 0.001) between antigen level and the severity of the disease as monitored by ultrasonography. We conclude that our ELISA may be a useful adjunct to other methods, such as ultrasonography, for monitoring the course of S. haematobium infection and treatment.