Because across-the-board data indicate that renin and cyclooxygenase-2 (COX-2) expression in the kidney cortex are regulated in parallel and because ANG II can inhibit COX-2 expression, the purpose of our study was to characterize a potential general inhibitory feedback of the renin-angiotensin system on renocortical COX-2 expression in vivo. Rats were fed a high-, normal-, or low-salt diet or were chronically infused with furosemide (60 mg. kg(-1). day(-1)) or the left renal artery was clipped, and the animals were treated in addition to or without the angiotensin-converting enzyme inhibitor ramipril (10 mg. kg(-1). day(-1)). A high-salt diet reduced expression of COX-2, whereas a low-salt diet, furosemide infusion, and renal artery stenosis stimulated COX-2 expression. Additional angiotensin-converting enzyme inhibition led to further increases in renocortical COX-2 expression by 62, 136, 300, 50, and 70% for a high-, normal-, and low-salt diet, furosemide infusion, and renal artery stenosis, respectively. Thus our data suggest a general inhibitory effect of the renin-angiotensin system on renocortical COX-2 expression.