Receptor binding studies have been carried out in guinea-pig cerebral cortex and gastric mucosa membrane preparations using 3H-cimetidine as the radioligand. The binding was found to be time dependent and saturable and confined to a single population of binding sites. However, the calculated K D values were different for the two tissues, did not correlate with those reported from classical pharmacological experimentation and there was either no or limited displacement by known H 2 specific agonists. It was concluded that the observed high affinity binding site was probably related to an imidazole recognition site rather than the histamine H 2 receptor. The need for careful evaluation of the data is stressed.