We describe the specificity and sensitivity of measuring a combination of basic CSF variables and Borrelia burgdorferi (Bb)-specific IgG and IgM antibody index (AI) values for the diagnosis of early neuroborreliosis. Basic CSF variables included total cell count, quantitation of activated B cells (IgG, IgA, and IgM classes), CSF/serum quotient diagrams for IgG, IgA, and IgM (to quantitate brain-derived immunoglobulin fractions in CSF), and CSF/serum albumin ratio as a measure of blood-CSF barrier function. The Bb-specific component of immunoglobulins in CSF and serum was quantitated by ELISA. Results are based on data from CSF and serum of 24 patients with definite neuroborreliosis, 45 patients with other neurologic diseases, and 28 control individuals. Combined evidence of an elevated CSF cell count, IgM-class dominance in both the cellular and intrathecal humoral immune response, and blood-CSF barrier dysfunction yielded 70% diagnostic sensitivity and 98% diagnostic specificity for detection of neuroborreliosis. Intrathecal production of Bb-specific IgM, evaluated as Bb-specific IgM antibody index (Bb-IgM-AI; pathologic value > 1.4) showed 79% diagnostic sensitivity and 96% diagnostic specificity. Correspondingly, elevated Bb-specific IgG antibody index (Bb-IgG-AI; pathologic value > 1.4) displayed 63% diagnostic sensitivity and 89% diagnostic specificity. Combined analysis of Bb-specific AI values and basic CSF variables gave the highest sensitivity (80%) and specificity (98%). Analysis of CSF variables over a disease course showed that acute versus past disease could be discriminated by a combination of basic CSF variables and Bb-specific AI.(ABSTRACT TRUNCATED AT 250 WORDS)