The haemodynamic effects of histamine infusions (0.5 to 8 g kg^–1 min^–1) were studied in anaesthetized dogs previously instrumented for measurements of left ventricular pressure (LVP),dP/dt _max, aortic and femoral blood pressure (P _AO;P _AF) and femoral blood flow (F _AF). Blockage of H₁- or H₂-receptors alone with either mepyramine (1 mg kg^–1 min^–1) or cimetidine (2 mg kg^–1 min^–1) did not prevent the dose-dependent decrease in contractility and blood pressure responses to histamine. Since, however, both antihistamines administered in combination competitively antagonized responses to histamine, it is concluded that peripheral and cardiac effects of histamine involve interaction with both H₁- and H₂-receptors. The potentiation ofdP/dt _max,P _AO andF _AF responses to histamine as produced by theophylline (4 mg kg^–1 min^–1) was completely reversed by cimetidine, which thus may be taken as an indication that also under in vivo conditions cyclic AMP serves as a mediator only for histamine H₂-responses. However, since these results do not allow clearly to separate between primary cardiac and peripheral responses in a further set of experiments blood pressure was held constant during histamine infusions. When peripheral mechanisms were excluded as responsible for cardiac actions of histamine by this procedure histamine evoked small positive inotropic responses which were prevented by cimetidine. These findings suggest that on ventricular muscle of dogs there exists a small fraction of H₂-receptors mediating positive inotropic effects which, however, were masked on intact animals by negative inotropic responses due to a pronounced fall in blood pressure.