Lindane pretreatment of isolated rat prostatic epithelial cells resulted in a time- and dose-dependent impairment of the stimulation of cyclic AMP levels by vasoactive intestinal peptide (VIP); the optimal conditions for producing this impairment were found to be 5 min of cell exposure to 0.2 mM-lindane at 25-degrees-C. The inhibitory effect of the insecticide was related to a decrease in VIP efficiency since the maximal cyclic AMP response (at 100 nM VIP) was about 50% of that in control cells. VIP potency was unaffected since the half-maximal cyclic AMP response was elicited at about 3 nM VIP in both the control and lindane-pretreated cells. The results indicate that lindane interferes with the cyclic AMP system in prostatic epithelium, and this could be a consequence of some interaction in the prostate gland between the two main systems for signal transduction (i.e. adenylate cyclase and phosphatidylinositol/Ca2+/protein kinase C).