The effects of chronic gentamicin administration on renal function was studied in dogs receiving 4 mg/kg i. m. of gentamicin b. i. d. for 28 days. Administration of gentamicin resulted in a bimodal change in renal function. A decrease in urine osmolality was first noted on day 6 and declined progressively throughout the study. This decrease in urinary concentrating ability was preceded by a steady rise in urinary prostaglandin E2 (PGE) excretion and followed by a rise in plasma renin activity (PRA). Prior to an increase in azotemia, urinary PGE decreased precipitously while PRA continued to rise throughout the remainder of the study. The precipitous decrease in GFR was accompanied by a significant increase in FENa to seven times control. These studies suggest a dual effect of chronic gentamicin administration on renal function: (1) an early effect manifested by stimulation of urinary prostaglandin production with a concomitant loss of urinary concentrating ability and mild prerenal azotemia, and (2) a late effect, preceded by a decrease in urinary prostaglandin excretion while PRA continues to increase, and manifested by increase fractional excretion of sodium and progressive azotemia.