The presence of interleukin-2 (IL-2) and soluble IL-2 receptors (sIL-2R) in the serum and cerebrospinal fluid (CSF) of patients suffering from multiple sclerosis (MS) has been extensively investigated. These studies, however, have produced conflicting results. The only significant finding concerns the frequent detection of increased sIL-2R levels in the serum in patients with relapsing-remitting MS (RRMS), especially after a short interval of time from the last relapse. Whether this finding can be used for clinical purposes requires further investigation. A standardization of the ELISA methods used to detect cytokines in biological fluids is urgently needed. Increased serum and/or CSF levels of IL-2 and sIL-2R strongly confirm a CD4+ Th1 activation.