The changes of the pulmonary arterial pressure (PAP) following microinjection of histamine (HA) into the lateral ventricle in the rabbit were investigated. It was found that (1) Intraventricular injection of HA (50 micrograms) induced either an increase (in the majority) or a decrease in PAP and cardiac output (CO), or a biphasic response characterized by a decrease followed by an increase. Slowing down of heart rate (HR) and elevation of carotid arterial pressure (CAP) were observed accordingly. (2) After bilateral cervical vagotomy or fixing the heart rate by cardiac pacing, drop in CO and PAP in response to HA was no longer observed. Instead, they even showed some constant increase. The pressor response of PAP and CAP to HA could be partially blocked by phentolamine applied intravenously without affecting the increment of CO. On the other hand, intravenous injection of propranolol could totally block the HA-induced increment of CO, but not affect the pressor responses of PAP and CAP. Intravenous injection of hexamethonium or combined application of phentolamine and propranolol could completely abolish all the increment responses in CO, PAP and CAP to HA. (3) The cardiovascular responses to HA could be blocked by the H1 receptor blocker-chlorpheniramine, but not by H2 receptor blocker-cimetidine. It is thus assumed that HA applied intraventricularly can activate the central H1 receptor, thus inducing an increase in the cardiac output and vasoconstriction of pulmonary and peripheral vessels giving rise to an elevation of both PAP and CAP by way of sympathetic nerve. Central application of HA also induces bradycardia by activating vagus nerve.(ABSTRACT TRUNCATED AT 250 WORDS)