Ca antagonists of dierent classes (verapamil, nifedipine, nicardipine, diltiazem) in a concentration of 10 À5 M and higher are known to suppress Ca 2 transport into the lymphocyte cytosol, changing a normal response of lymphocytes to mitogens and antigens and so inhibiting their proliferation, as well as IL-2-induced cell proliferation, and their receptor expression on the surface of lymphocytes without cell cytotoxicity. In the present work we studied the eect of some 1,4-dihydropyridines (DHP) such as nimodipine, nicardipine, nifedipine, niludipine, cerebrocrast, etaftoron, as well as metabolites of cerebrocrast: compounds 7 and 8, ( four of the last were synthesized in the Latvian Institute of Organic Synthesis) on rat spleen isolated lymphocyte activation and proliferation in vitro following stimulation with the mitogens concanavalin A (Con A) and recombinant interleukin-2 (IL-2), insulin and insulin antibodies. Based on the experimental results we conclude that in low concentrations (10 À7 to 10 À9 M) the tested 1,4-DHP Ca antagonists stimulated the process of rat spleen lymphocyte proliferation and DNA synthesis, especially cerebrocrast. It is proposed that these Ca antagonists, as well as causing a concentration decrease of Ca 2 , also activated phosphodiesterase, which in its turn, suppressed cAMP accumulation in the lymphocytes and eventually increased Ca 2 ion transport in the cells. Cerebrocrast among all the studied DHP Ca antagonists was the most potent in studies of activation of the lymphocytes in the presence of Con A, IL-2 and insulin, which indicates the number of suppressor and helper lymphocytes and formation of insulin and interleukin receptors on their membrane surface. The increase in the lymphocyte suppressive activity produced by this compound eect can prevent diabetes mellitus types I and II at the stages of pre-diabetes, early and distant diabetes, from hyperexpression of insulin and its receptor antibodies.