Although interleukin (IL)-10 inhibited lymphocyte proliferation in mixed lymphocyte cultures (MLC) and blocked stimulation of alloreactive T cell clones (TCC) by peripheral blood mononuclear cells (PBMC), the cells surviving culture with IL-10 showed enhanced viability. A minority of IL-2-dependent T cell lines, moreover, incorporated tritiated thymidine when cultured with IL-10 alone; their proliferation with IL-10 was dose-dependent, prevented by addition of neutralizing antisera to IL-10 but not to IL-2 and/or IL-4 and observed both shortly (4 days) and later ( 7-10 days) after T cell allostimulation. Examination of the proliferative responses to IL-10 of a panel of TCC revealed heterogeneity of responsiveness: whereas only one of five CD8(+) TCR2 (T cell receptor alpha, beta)TCC proliferated with IL-10, three of five CD4(+) TCR2-TCC proliferated, one of them strongly. In contrast, all three TCR1 (gamma delta)-TCC tested responded to IL-10, albeit rather weakly. These results therefore suggest that in addition to its well-established inhibitory action on T cell activation, IL-10 may also exert positive influences on clonal expansion of subsets of preactivated T cells.