To our knowledge, the long-term effects of prazosin hydrochloride, an alpha 1-adrenoceptor antagonist, on renal function and body fluid composition have not been previously reported. Fourteen hypertensive men in whom the BP was normalized with prazosin monotherapy, underwent assessment of renal function and body fluid composition following short-term (three to six weeks), long-term (five to six months), and withdrawal (two weeks) therapy. Neither short- nor long-term prazosin therapy had any adverse effect on the glomerular filtration rate or effective renal plasma flow. Renal vascular resistance was decreased 14% during short-term therapy, but not during long-term therapy. Urine flow rate, urine osmolality, free water clearance, and fractional sodium and potassium excretions were statistically unchanged throughout drug therapy. Plasma volume and extracellular fluid volume were increased following both short- and long-term therapy. Long-term prazosin monotherapy effectively lowers BP without resulting in drug tolerance, however, sodium retention probably limits its antihypertensive effectiveness.