Seven different formulae and agarose isoelectrofocusing (AIF) using immunolabelling for IgG were compared for their ability to discriminate between intrathecally produced IgG and transudated IgG in cerebrospinal fluid. All reference limits were set to a specificity of 97.5% (reference group, n = 211). The probability of a positive test (p+) was evaluated for 112 patients with multiple sclerosis (MS), 42 with meningitis, 114 with noninflammatory diseases affecting the central nervous system (CNS), 23 with Guillain-Barré syndrome, and 56 with various diseases not affecting the CNS. Agarose isoelectrofocusing had the best diagnostic sensitivity (93%) for MS, combined with a low p+ (0-19%) for other diseases. Among the formulae, the IgG extended index and Reiber's hyperbolic formula were equivalent, giving high (75-79%) diagnostic sensitivity for MS combined with low p+ (4-22%) for other diseases. All other formulae, although sensitive for MS, had a higher rate of false positive results.