1. Renal function was studied in 50-, 70-, 90- and 200-day-old rats with essential fatty acid deficiency. The pharmacokinetics of tobramycin was investigated in 90-day-old essential fatty acid-deficient rats. 2. A higher glomerular filtration rate and a higher serum concentration of urea were seen in 50-day-old essential fatty acid-deficient rats compared with age-matched controls. Later, the glomerular filtration rate progressively deteriorated in parallel with a decline in effective renal plasma flow and with a concomittant rise in serum levels of urea and creatinine. The serum concentration of protein was lower in the rats with essential fatty acid deficiency and that of sodium was higher than in the control rats. The non-renal clearance of tobramycin was increased in the rats with essential fatty acid deficiency. 3. The early hyperfiltration in essential fatty acid-deficient rats with the subsequent fall in glomerular filtration rate, which was paralleled by a rise in serum levels of urea and creatinine, as well as the increased non-renal clearance of tobramycin, are in accordance with the clinical manifestations of cystic fibrosis. Rats with essential fatty acid deficiency might be a useful model with which to study the pathophysiological renal changes in cystic fibrosis related to the progressive essential fatty acid deficiency in this disease.