Cigarette smoking has been shown to cause profound suppression of T-cell responses in the lungs, but the mechanism by which this phenomenon occurs is not known. We have shown that 10 microM p-benzoquinone (p-BQ), a thiol-reactive benzene derivative found in cigarette tar, inhibits mitogen-induced IL-2 production by human peripheral blood mononuclear cells by 76 +/- 7% without affecting lymphocyte/macrophage agglutination or blast transformation. The effect of p-BQ appeared to be specific for IL-2 production, since de novo induction of the IL-2 receptor alpha-chain (CD25) and ICAM-1 (CD54) and upregulation of LFA-1 alpha/beta (CD11a and CD18) were unaffected. In contrast, N-ethylmaleimide (NEM), another alpha,beta-unsaturated diketone with thiol-reactive properties similar to those of p-BQ, inhibited all of these Con A-induced activation events. These results suggest that p-BQ inhibits T-cell mitogenesis by blocking a thiol-dependent event that controls IL-2 production but not other T-cell activation events.