The injection in rats of 4 mg/kg gentamicin results in accumulation and continued presence of the antibiotic in the renal parenchyma compared with its rapid elimination from other tissues. With repeated injections at 24-hour intervals over a period of 3 weeks, gentamicin concentrations in the cortex reach 356 +/- 139 microgram/g after 1 week of treatment, i.e. levels 50 times higher than the maximum serum levels. They then stay at a saturation plateau before decreasing very slowly to levels of 50 microgram/g 2 weeks and 15 microgram/g 15 weeks after the last injection. The accumulation takes place mainly in the cells of the proximal convoluted tubule. In the medulla, gentamicin behaves similarly but the levels are lower. Weeks after the last injection, urine levels of gentamicin are still appreciable. In spite of this enormous accumulation, the treatment does not result in disturbance of renal function or striking morphological changes. These observations are based on dosages of gentamicin corresponding to those used clinically. Compared to earlier observations based on the supratherapeutic administration of the antibiotic, the present study provides a better understanding of the mechanisms involved in gentamicin nephrotoxicity.