Increasing body of evidence which suggests a crucial role for interleukin (IL)-12 in modulating immune responses in multiple sclerosis (MS) prompted us to analyze IL-12 in serum from MS patients. We measured the sera concentrations of IL-12, tumor necrosis factor (TNF)-alpha and transforming growth factor-beta1, in 21 MS patients and 13 patients with non-inflammatory nervous diseases. In clinically active MS, serum levels of IL-12 were detectable in 53% and TNF-alpha in 40% of patients. None of the patients with clinically inactive MS had detectable IL-12 and TNF-alpha sera levels. Analysis of serum concentrations of all three cytokines revealed no significant differences between MS patients and controls. These findings provide further evidence that both IL-12 and TNF-alpha might have an active role in immunopathogenesis of MS.