We have studied the in vitro mitogenic effect of ZnCl2 in cultures of lymphocytes from Balb/c or C57BL/6 mice which are high-responder or low-responder to T-cell mitogens respectively. Zn induced proliferation of spleen cells from Balb/c mice cultured without 2-ME. Higher levels of proliferation were observed in cultures with 2-ME. In contrast, Zn only induced proliferation of spleen cells from C57BL/6 mice in the presence of 2-ME. No response to Zn was observed in cultures without 2-ME, of spleen cells from either Balb/c or C57BL/6 mice depleted of plastic adherent cells. However, in cultures with 2-ME, Zn induced proliferation of non-adherent as well as plastic adherent cells from either strain of mice. In cultures without 2-ME, Zn induced proliferation of thymocytes from Balb/c mice, whereas did not show constant mitogenic effect on thymocytes from C57BL/6 mice. In contrast, Zn determined higher levels of proliferation of thymocytes from either strain of mice when cultured with 2-ME. Zn had earlier and stronger mitogenic effect on mature thymocytes of either strain of mice than in total thymocytes, both in cultures with or without 2-ME. However, Zn did not induced proliferation in cultures of immature thymocytes of either strain of mice.