Several laboratories have reported ligand binding studies using radioactive histamine H1antagonists to label the H1receptors in mammalian brain. We have extended these studies to a detailed examination of the binding of [3H]mepyramine to monkey brain and have shown that the distribution is similar to that in man, with specific binding sites being concentrated in the frontal cortex with relatively low binding to the pons and basal ganglia. The binding shows a single saturable component with aKDof about 1 nMand a Hill plot slope close to unity. These observations are the same for all structures tested. Comparison with data from other laboratories suggests that in this species, the histamine receptor is the same as that in peripheral tissues. FromKivalues for various ligands and comparison ofKDestimates in other species, the receptor seems to be essentially identical to the H1receptor in central and peripheral tissues of the guinea pig and also to that in human brain. The rat and possibly the dog have minor differences from the monkey in terms ofKDvalues for [3H]mepyramine binding.