We have analyzed the effect of Cyclosporin‐A (CsA) on the in vitro suppression of Epstein‐Barr virus (EBV)‐induced B‐cell proliferation exerted by autologous T‐lymphocyte subpopulations separated on the basis of cell density. CsA abolished the growth‐inhibitory capacity of high‐density T cells but influenced only marginally the activity of low‐density lymphocytes; this suggested that different mechanisms mediate suppression in the two subsets. Stimulation with irradiated EBV‐transformed cells had a different impact on the activity of low‐ and high‐density lymphocytes. Proliferative and cytotoxic responses were inversely correlated, i.e. high‐density cells proliferated but exerted low cytotoxicity, while the lytic activity of the low density subset was stronger in the absence of significant cell proliferation. Proliferation and generation of cytotoxicity were abrogated by CsA in both subsets. The activities could be restored by addition of exogenous IL‐2, suggesting that the drug may interfere with the cascade of lymphokine–cell interactions which leads to activation of immune responses. From the analysis of the CsA effects on the two subsets it seems that the high‐density one contains specific memory T cells which are activated and proliferate upon encounter with EBV‐infected cells. On the other hand, low‐density lymphocytes are induced to release soluble factors with antiproliferative activity. The secretory function was resistant to the suppressive effect of CsA.