In this work, the effects of vasoactive intestinal peptide (VIP) in a concentration range from 10(-13) to 10(-7) M were studied in vitro on two common activities of peritoneal rat lymphocytes and macrophages: adherence and mobility (spontaneous and chemotaxis). The results show that VIP stimulated the adherence of the two cells studied, and increased the macrophage mobility but decreased this activity in lymphocytes. Moreover, a specific protein kinase C (PKC) activator such as phorbol myristate acetate (PMA, 50 ng/ml) also stimulated significantly the adherence and chemotaxis of both macrophages and lymphocytes. By contrast, a PKC inhibitor, retinal (2 x 10(-5) M), decreased significantly these capacities. Macrophages incubated with both VIP and PMA in relation to those incubated with VIP or PMA showed an increase in adherence and chemotaxis, whereas in lymphocytes adherence was also increased but chemotaxis decreased. The incubation with forskolin (10(-5) M), an enhancer of intracellular cAMP levels, produced an inhibitory effect of the chemotaxis activity in both types of cells. VIP prevented this inhibitory effect of forskolin in macrophages but not in lymphocytes. In addition, VIP was chemoattractant for macrophages but not for lymphocytes. The present study proves that VIP proves that VIP has a coronary effect on the two principal and representative types of immune cells in the rat peritoneum: lymphocytes and macrophages, stimulating macrophage chemotaxis through PKC activation and inhibiting lymphocyte chemotaxis through adenylate cyclase activation.