Cerebrospinal fluid (CSF) and serum levels of interleukin-2 (IL-2), soluble IL-2 receptors (sIL-2R), neopterin, L-tryptophan (L-TRP) and beta 2-microglobulin (beta 2-M) were measured in 31 untreated multiple sclerosis patients in acute exacerbation and 27 normal controls. Twenty-six patients showed the relapsing-remitting type of disease (RRMS); 5 had a chronic-progressive course (CPMS). No changes in serum IL-2 and sIL-2R were found between RRMS patients and controls, whereas serum and CSF levels as well as the CSF/serum ratio of neopterin were significantly elevated in the RRMS group. IL-2 was not detectable in CSF of patients or controls and sIL-2R levels were at the level of the lower detection (LD) sensitivity of the ELISA method. Four of 23 RRMS patients versus 1 of 25 controls showed CSF sIL-2R levels above the LD sensitivity, indicating a trend towards elevation in acute relapse. No difference was found in serum and CSF L-TRP and beta 2-M of patients and controls. In CSF of RRMS patients neopterin and L-TRP correlated negatively, reflecting the interferon-gamma mediated activation of macrophages in acute relapse. A significant positive correlation (Spearman rank 0.57, P = 0.001) between serum IL-2 levels and duration of acute relapse (mean 30 days) warrants further evaluation.