The sensitivity of stool examination techniques used in establishing a diagnosis of infection with Schistosoma mansoni is variable. Thus, in comparative studies of immunodiagnostic tests the sensitivity of the reference stool examination technique used is a major determinant of the specificity of the tests being evaluated. Our study verified the foregoing when we evaluated six different serodiagnostic tests by comparing their results to those of a sensitive stool examination method, the modified Ritchie formol-ether concentration test (MRCT). Additionally, the relationship between S. mansoni infection intensity and the sensitivity and specificity of the serologic tests was studied. Serum samples from 122 randomly selected residents of Parcelas de Boquerón, Puerto Rico, were tested blindly for S. mansoni antibodies with the following tests: (a) indirect immunofluorescence (IIF) with cercariae and/or cryostat sections of adult worms; (b) slide flocculation with cercariae as antigen; (c) Ouchterlony immunodiffusion with extracts of cercariae or adult worms; and (d) circumoval precipitin (COP) test with fresh eggs as antigen. Seventy-three (59.8%) of the 122 individuals tested were infected with S. mansoni, and the geometric mean egg output of positive individuals was 3.5 eggs per gram of feces. The COP test was 95% sensitive, and 96% specific in detecting S. mansoni antibodies, while the second best test, IIF with extracts of adult worms, was 73% sensitive and 86% specific. A single COP test detected 69 of the 73 infected individuals, while a single MRCT detected only 51. Thus with a single MRCT as reference, the COP was only 66% specific, but when three or more MRCT's were performed, the specificity increased to 96%. Additionally, the COP test was the only one reaching a level of 100% sensitivity at average egg excretion levels of ten or more eggs per gram. A graphical model of the relationship between prevalence of infection by serology and by multiple stool examinations, and an index for evaluating the performance of serologic tests relative to a standard reference are presented.