Willoughby and Willoughby (1,2) have demonstrated that the presence of mitogens in inhaled environmental pollutants increases the inflammatory response mounted by the lungs. Here we report that condensed tannins, a major component of cotton milldust, are potent mitogens for human peripheral blood T-lymphocytes in vitro. Tannin causes the time and dose dependent proliferation of human T-lymphocytes. A maximal proliferative response occurs at a tannin concentration of 100 pg/mL and is essentially equivalent to the proliferative response to a maximal dose of the well characterized T-mitogen, Concanaval in A. The time course for tannin induced T-lymphocyte proliferation is similar to that for other mitogens. Also like other mitogens, monocytes are required for a maximal response. Aqueous cotton dust extract also is mitogenic for human T-lymphocytes. However, the proliferative response was lower than predicted on the basis of its tannin content. Activation of T-lymphocytes present in the airways by tannin could result in mediator production that contributes to the pathogenesis of byssinosis.