Palmitoyl carnitine and lysophosphatidylcholine have been implicated in the generation of cardiac arrhythmias in the ischemic myocardium. These amphiphilic compounds are structurally similar to platelet-activating factor (PAF). The present study compared the hypotensive effect of these compounds to PAF in the anesthetized rat. Palmitoyl carnitine was about 1000 times less potent than PAF in lowering the blood pressure. Lysophosphatidylcholine and other structurally related compounds, in dosages similar to that of palmitoyl carnitine, had no significant hypotensive action. CV 3988, a PAF antagonist, blocked the hypotensive action of PAF but had no effect on the hypotensive action of palmitoyl carnitine. This suggested the effect of palmitoyl carnitine was not associated with the same site or mechanism as PAF. The results also ruled out the involvement of prostaglandin formation and of the sympathetic nervous system since indomethacin, phenoxybenzamine and propranolol did not affect the hypotensive action of palmitoyl carnitine. In addition, it is unlikely that palmitoyl carnitine exerted its effect by a direct membrane-perturbing action because lysophosphatidylcholine, which possesses similar amphiphilic properties, does not share the same hypotensive effect.