The release of histamine, eicosanoids and catecholamines were measured after induction of anaphylaxis in isolated guinea-pig hearts. The concentration-time profile of these mediators was compared with changes of cardiac parameters. The histamine and catecholamine levels of the coronary effluent were determined at 10 s intervals; thromboxane and prostacyclin levels at 60 s intervals. The release of histamine and norepinephrine were maximum between 20 and 30 s after the antigen challenge and decreased rapidly within 60 s. Thromboxane and prostacyclin increased to a maximum after 3 min and declined slowly within 10 min. The rise in histamine release was correlated with tachycardia. The release of thromboxane was correlated with the increase of coronary perfusion pressure. Cimetidine inhibited the tachycardia and clemastine reduced bradyarrhythmia. The inhibition of lipoxygenase and cyclooxygenase also reduced the rise in the perfusion pressure. These data suggest that different mediators are time-dependently involved in anaphylaxis-induced cardiac changes.