Immunologic immediate hypersensitivity reactions of the heart are characterized by tachycardia and arrhythmias caused by the release of endogenous cardiac histamine. The contribution of SRS-A to anaphylactic cardiac dysfunction was indirectly assessed by the use of the selective SRS-A receptor antagonist FPL 55712. In the presence of FPL 55712 the concentration-response curves for the chronotropic and arrhythmogenic effects of endogenous cardiac histamine were progressively shifted to the right as a function of the concentration of FPL 55712. Moreover, the duration of the positive chronotropic effect of endogenous cardiac histamine was shortened by FPL 55712. On the other hand, FPL 55712 failed to reduce the chronotropic and arrhythmogenic effects of exogenous histamine. Partially purified histamine-free SRS-A obtained from rat peritoneau potentiated and greatly prolonged the positive chronotropic effect of exogenous histamine. Potentiation and prolongation were both blocked by FPL 55712. Thus, our results suggest that SRS-A sensitizes the heart to the tachyarrhythmic effects of histamine.