In the isolated perfused rat heart cardiac rate and contractility are directly affected by 4 naturally occurring cannabis constituents, .DELTA.9-tetrahydrocannabinol, .DELTA.8 -tetrahydrocannabinol, cannabinol and cannabidiol. All the drugs depressed myocardial contractility. Their effect on rate, however, was not uniform: .DELTA.8-tetrahydrocannabinol produced cardiac arrhythmias but no other consistent change; both .DELTA.9-tetrahydrocannabinol and cannabinol caused tachycardia; cannabidiol produced bradycardia, arrhythmias and asystole. As a consequence of the disposition of the cannabinoids to accumulate in the isolated heart, high tissue concentrations appeared in conjunction with the direct cardiac effects.