Tuberal hypothalamic tissue cultures were used to investigate the actions of histaminergic agents on neuronal activity using extracellular glass micropipettes. Histamine and H1- and H2-agonists were applied locally onto single active neurons by iontophoresis, while histaminergic antagonists were perfused through the bathing medium. Peri-event histogram and ratemeter analysis showed histamine to both excite and depress unit activity. Excitations were only antagonized by putative H1- and not H2-histamine antagonists, whereas inhibitions were antagonized by H2- and H2-antagonists. Dimaprit, a specific H2-agonist, elicited inhibitions of activity, while 2-(2-pyridyl)ethylamine, a putative H1-agonist, elicited both excitations and inhibitions. Two pharmacologically distinct populations of histamine receptors may exit in the hypothalamus: excitatory H2-receptors and inhibitory H2-receptors.