1. Effect of histamine (HA) (10(-4)-10(-2) M) on spontaneously beating rat atrium was investigated. HA produced a biphasic effect which is composed of an initial negative chronotropy followed by a positive chronotropic phase, at each single dose. 2. At a submaximal dose of HA (3 x 10(-3) M) we have investigated the effects of some antagonists on the biphasic effect profile. 3. Propranolol (10(-7) M) depressed the secondary phase by abolishing the biphasic pattern of the effect of HA leading it to a monophasic one (negative chronotropy). 4. On the other hand, combination with atropine (10(-7) M) was shown to reduce the negative inotropic effect (in the secondary phase) which was produced by HA in the presence of propranolol. 5. The initial negative chronotropic phase was significantly enhanced by propranolol and reduced by pheniramine (10(-6) M). 6. Pheniramine also potentiated the positive chronotropy at the secondary phase of the response, but cimetidine (10(-4) M) has no significant effect on both phases. 7. Theophylline (10(-4) M) abolished the initial negative chronotropic phase, but did not influence the secondary phase. Dipyridamole (10(-5) M) did not affect the secondary phase of the response of HA, but increased the initial negative chronotropic effect.