Serum and urine levels of two Schistosoma circulating antigens, the circulating anodic antigen (CAA) and the circulating cathodic antigen (CCA), were determined by monoclonal antibody-based enzyme-linked immunosorbent assays in 56 Egyptian patients infected with S. mansoni and in 12 patients infected with both S. mansoni and S. haematobium. Both CAA and CCA could be specifically demonstrated in 82% and 88% of the serum samples and in 88% and 87% of the urine samples, respectively. While complete specificity was maintained, sensitivity was increased to a range of 91–98% by parallel use of the two circulating antigen assays, i.e., an individual with a positive titer for at least one of the assays was considered to be infected. A combination of CAA and CCA determinations in urine samples only resulted in a sensitivity of 94%. However, the highest sensitivity was achieved when the serum-CCA assay was combined with the urine-CCA assay (98%) or with the urine-CAA assay (97%). Sensitivity could not be increased further by combining more than two tests. A significant correlation was demonstrated between the level of circulating antigen and the number of parasite eggs in feces in each of the four assays. In addition, the levels of CAA and CCA in serum and urine were significantly correlated with each other. Our results indicate that diagnosis of schistosome infections by detection of circulating antigens can be significantly improved by parallel testing for multiple antigens.