Minocycline has been shown to have an anti-inflammatory effect in patients with rheumatoid arthritis (RA). Since there is evidence that RA is a T cell-mediated disease, we investigated the effect of minocycline on human T cell clones derived from the synovium of an RA patient. The T cells, when activated via the T cell receptor (TCR)/CD3 complex, were suppressed functionally by minocycline, resulting in a dose-dependent inhibition of T cell proliferation and reduction in production of lL-2. interferon-gamma (IFN-γ) and tumour necrosis faetor-alpha (TNF-α). Besides an inhibition of IL-2 production, mitiocycline exerted its effect on T cell proliferation by induction of a decreased IL-2 responsiveness. We showed that the chelating capacity of minocycline plays a crucial role in the inhibitory effect on T cell function, since the inhibitory effect on T cell proliferation could be annulled by addition of exogenous Ca²⁺. However, minocycline did not markedly influence the typical TCR/CD3-induced intracellular Ca²⁺ mobilization. Taken together. the results clearly indicate that minocycline has immunomodulating effects on human T cells.