The effects of fatty acyl coenzyme A (CoA) esters (palmitoyl-, stearoyl-, oleoyl-, linoleoyl- and arachidonoyl--CoA) on the activities of lipoxygenase and cyclooxygenase in rabbit platelets were examined. Palmitoyl-, stearoyl-, oleoyl- and linoleoyl- CoA were potent inhibitors of platelet lipoxygenase activity. In addition to the lipoxygenase, the four fatty acyl-CoA esters elicited inhibitory activity on platelet cyclooxygenase, although the inhibition was a little weaker. The CoA derivative of the icosanoid precursor arachidonic acid (AA) showed little inhibition on lipoxygenase and cyclooxygenase. Palmitic, stearic and oleic acids had little or no effect on lipoxygenase and cyclooxygenase, in contrast with their CoA derivatives. Linoleic acid was more potent than linoleoyl-CoA as an inhibitor of the cyclooxygenase, but it was a weak inhibitor of the lipoxygenase. These results suggest that the CoA derivatives of palmitic, stearic, oleic and linoleic acids have the potential to modulate both platelet lipoxygenase and cyclooxygenase activities and may have functional effects within platelets.