Evidence for and against heterogeneity in the histamine H2-receptor population is reported: it was based on different degrees of potency and also of efficacy among the H2-receptor-selective agonists; less striking but still evident differences in the potency of H2-antagonists; atypical interactions between H2-agonists and antagonists in particular experimental conditions and finally inability of H1- and H2-receptor antagonists to block some of the effects of histamine. Binding studies gave equivocal results. All the data reported in this review suggest that, although it is premature to speak about H2-receptor subtypes, further investigations are needed to check whether or not H2- and perhaps also H1-receptors represent homogeneous populations of histamine receptors.