To compare four ways of measuring CSF IgG levels in diagnosing multiple sclerosis (MS), we analyzed CSF samples of 106 patients with clinically definite, probable, or possible MS and 127 patients with other diseases. The IgG synthetic rate and IgG index were the most sensitive tests at 0.88 and 0.94, respectively; IgG alone and IgG-albumin ratio, at 0.53 and 0.59, were less valuable. The IgG synthetic rate (0.87) was more specific than the IgG index (0.73), making it the quantitative measure that best correlated with a clinical diagnosis of definite MS. However, combining these four methods showed an even higher correlation. Quantitative CSF IgG elevations occurred much less frequently in patients with clinically definite MS receiving immunosuppressives and in those with clinically probable and possible MS. We did not perform qualitative CSF IgG measurements, but our methods' sensitivity and specificity were comparable with those attributed to oligoclonal IgG bands by others. We also found numerous other diseases where elevations of CSF IgG occurred by all four methods.