The effects of histamine and specific histamine agonists has been examined on isolated longitudinal colon strips of guinea-pig and rat. Histamine and 2-pyridyl-ethylamine but not 4 methylhistamine produced a concentration-related contractile response in the guinea-pig colon. The H1-antagonist clemizole antagonized competitively the effect of histamine but the H2-antagonist ranitidine did not modify the dose-response curve to histamine in the guinea-pig colon. Atropine, hexamethonium, prazosin and propranolol failed to modify the contractile response to histamine. Tone induced with KCl in guinea-pig isolated colon was not modified by histamine agonists even in tissues pretreated with clemizole or ranitidine. Histamine and histamine analogues were without effect on the isolated longitudinal strip of the rat colon. It is concluded that histamine produced dose-dependent contractions of the guinea-pig colon due to direct activation of H1-histamine receptors. There is no evidence in favour of the existence of H2-histamine receptors in this preparation. The lack of effect of histamine agonists in rat colon strip argues against the existence of histamine receptors in this preparation.