Treatment with interferon-beta reduces relapse rate, slows progression of neurological disability and reduces the number of active brain lesions observed with magnetic resonance imaging in relapsing-remitting multiple sclerosis. Interferon-beta has antiviral properties, but in addition it affects the expression of several immunoregulatory genes, including genes for cytokines such as interferon-gamma and interleukin-10. Cytokines are believed to be central in the pathologic process in multiple sclerosis, by regulating autoreactive T- and B-cell responses. In this study we have determined effects of interferon-beta on the frequency of cells in peripheral blood and cerebrospinal fluid expressing mRNA for interferon-gamma, tumor necrosis factor-alpha, interleukin-4 and interleukin-10 in a group of multiple sclerosis patients. All patients were treated for two months or more, since the beneficial effect of interferon-beta is not apparent until after several months of treatment. We detected a significant reduction of interleukin-10 mRNA expressing cells in the peripheral blood during interferon-beta treatment compared with pretreatment values (10 vs 33 cells/10(5); p = 0.028) while the other investigated cytokines were not significantly affected. We conclude that there is a long term effect of interferon-beta on cytokine expression in multiple sclerosis patients. Its relation to the therapeutic effect is as yet not clear.