The role of serological tests on cerebrospinal fluid (CSF) in the diagnosis of neuroschistosomiasis has not been fully elucidated; the condition is essentially diagnosed on the basis of circumstantial evidence, which may lead to an erroneous diagnosis, especially in highly endemic areas. We therefore carried out a prospective case-control study in which we compared the concentrations of immunoglobulin G (IgG) specific for schistosome soluble egg antigen (SEA) present in the CSF of 54 patients with schistosomiasis mansoni myeloradiculopathy (SMMR) with those observed in a control group consisting of 41 patients with epidemiological and serological evidence of exposure to schistosomes, and with other neurological disorders that result in mild to moderate impairment of the blood-brain barrier. Anti-SEA IgG was estimated by an enzyme-linked immunosorbent assay. The sensitivity, specificity and positive and negative predictive values were 56%, 95%, 94% and 62% respectively. Likelihood ratios and the corresponding post-test probabilities were determined for 4 levels of anti-SEA IgG in CSF. A value below 0.1 mu g/mL practically excluded the possibility of SMMR (post-test probability < 5%), a value above 1.4 mu g/mL practically confirmed the diagnosis of SMMR (post-test probability > 96%), values of 0.1 to 0.5 mu g/mL had no diagnostic value (post-test probability approximately 45%), and values of 0.6 to 1.4 mu g/mL were useful in some situations (post-test probability approximately 70%). We conclude that the estimation of anti-SEA IgG in the CSF is useful for the diagnosis of SMMR.