In cultured smooth muscle cells of rat aorta, four diuretic agents, furosemide, bumetanide, cicletanide and piretanide (all at 10(-6)-10(-5) M), significantly enhanced the transformation of exogenously added arachidonic acid (AA) to prostacyclin. Studies with cultured smooth muscle cells and human leukocytes revealed that these same agents failed to inhibit lipoxygenase pathways. Taken together, these results indicate that the diuretic properties of these agents might be associated with a general activation of the AA cascade.