The effect on kidney damage of the season of year at which gentamicin was administered to rats was studied. Rats received a single intramuscular dose of 200 mg/kg gentamicin at four different times of the day (08.00, 14.00, 20.00 or 02.00 hours. Studies were carried out in January-February, March-April, June-July and October-November. The nephrotoxicity was assessed by the increase of three urinary enzymes: two brush border enzymes, gamma-glutamyl transferase and alanine aminopeptidase, and a lysosomal enzyme: N-acetyl-beta-D-glucosaminidase. The results show that when the injection is administered at 20.00 hours in the January-February and the October-November studies and at 08.00 hours in the March-April study and at 14.00 hours in the June-July study there is a significant increase in the excretion of these enzymes. The renal toxicity of gentamicin therefore has circadian variations as well as seasonal variations. The peak enzyme level is displaced from the start to the end of the rest period of rats depending upon the time of year.