Cercarial elastase (CE) is one of the first proteins released in the host by invading schistosome cercariae. An enzyme-linked immunosorbent assay (ELISA)-formatted immunoassay has been developed to detect antibodies to the stage-specific CE antigen of Schistosoma mansoni as marker of exposure. We have evaluated this test system as an epidemiologic tool, using well-characterized sera collected from S. mansoni- and S. haematobium-infected subjects residing in endemic areas and from control subjects living in nonendemic areas in Egypt. Urine, stool specimens, and blood samples were collected from a sample of 272 endemic subjects randomly selected to represent different age groups in the range of 2–20 years of age. Of 47 S. mansoni-infected subjects, 41 (87.2%) had anti-CE IgG antibodies. Of 52 S. haematobium-infected cases, 38 (73.0%) had IgM antibodies to CE and 43 (82.7%) had IgG antibodies to CE. Of 173 egg-negative people in the endemic area, 84 (48.6%) were IgM positive and 99 (57.2%) were IgG positive. The mean IgM and IgG antibody levels were similar in the infected groups but were significantly lower in the egg-negative group (P = 0.001). All sera from young children (2–3 years of age) were uniformly ELISA negative. The prevalence of IgM and IgG antibodies to CE in children less than six years of age were significantly lower than in other age groups. There was no significant difference in prevalence rates of IgM and IgG anti-CE antibodies between subjects having other parasites present in the endemic area (Ascaris lumbricoides, Entrobius vermicularis, Hymenolepis nana, H. diminuta, Trichostrongylus spp., and Entamoeba histolytica) and those without any parasitic infection. All nonendemic sera (58), including those with other helminth infections, were uniformly ELISA negative for antibodies to CE. These findings suggest that antibodies to elastase indicate exposure, but not necessarily active schistosome infection.