Cicletanine, a new antihypertensive, slightly diuretic, drug was tested for its effects on arachidonic acid (AA) metabolism in cultured smooth muscle cells from rat aorta. Cicletanine significantly enhanced the production of prostacyclin from both exogenously added arachidonic acid and endogenous sources. This effect is not mediated through inhibition of the lipoxygenase pathways and occurs despite a slight but definite inhibition of the activity of acyl hydrolase. Taken together, these results indicate that the antihypertensive properties of cicletanine might be associated, at least in part, with activation of the AA cascade through the cyclooxygenase pathway.