The aim of this study was to demonstrate histamine-H2 receptors in glomeruli isolated from rat renal cortex and to correlate binding to stimulation by histamine of glomerular cyclic AMP concentration. Binding studies were performed at 10-12 degrees C using [3H]cimetidine as a tracer. Specificity of binding relies on the following: inhibition of [3H]cimetidine binding by the unlabelled drug, other H2-antagonists and agonists in contrast with the very weak inhibitory effects of H1 agonists and antagonists; reversibility of steady-state binding after addition of unlabelled drug; half inhibition of the glomerular cyclic AMP response to histamine at concentrations of cimetidine close to the KD value derived from the binding studies (3 microM); calculated KD value in agreement with the therapeutical concentration of cimetidine and the physiological concentration of histamine. [3H]Cimetidine binding concentration of cimetidine and the physiological concentration of histamine. [3H]Cimetidine binding strikingly increased in the presence of copper chloride (20-300 microM) due to an increase both in number of sites and affinity. However this greater binding did not influence either the inhibitory effect of cimetidine on histamine-induced glomerular cyclic AMP concentration or the stimulatory effect of histamine itself. [3H]Cimetidine binding was temperature-dependent since it progressively diminished from 0 to 37 degrees. This was not due to [3H]cimetidine degradation as shown by thin layer chromatography but rather to a change in drug-receptor interaction at higher temperatures. Glumerular concentration of cyclic AMP increased progressively in the presence of histamine (0.1-1000 microM). This stimulatory effect was markedly inhibited by H2 antagonists. These data demonstrate the presence in rat glomeruli of H2 receptors linked to adenylate cyclase.