Bioassay-directed fractionation of the methanolic extract of seeds of Casimiroa edulis led to the isolation of seven constituents with cardiovascular activity, namely the new compound synephrine acetonide and the known compounds N-monomethylhistamine, N,N-dimethylhistamine, proline, N-methylproline, gamma-aminobutyric acid and casimiroedine. In anesthetized rats, both histamine derivatives produced transient hypotension mediated via H1-histaminergic receptors and in the case of N,N-dimethylhistamine, via nitric oxide release. Synephrine acetonide produced transient hypertension and tachycardia, mediated via alpha- and alpha- and beta-adrenergic receptores, respectively. The chromatographic zone containing N-methyproline, proline and gamma-aminobutyric acid elicited marked and prolonged hypotension. Finally, casimiroedine did not modify the blood pressure of anesthetized rats, but lowered it persistently in anesthetized guinea pigs. It was concluded that hypotension produced by C. edulis is due to several active components. The immediate effect can be attributed to the histamine derivatives acting on H1-receptors. More prolonged hypotension would be produced by the mixture of amino acids through an unknown mechanism, as well as by casimiroedine, possibly by activation of H3-receptors. Hypotension is partially offset by synephrine acetonide through adrenergic mechanisms.