Previous data have suggested an age-related increase in renal clearance of gentamicin. This phenomenon could be the result of an increase in glomerular filtration rate (GFR) and/or of an augmentation in its transtubular influx. To investigate this question, four groups of rats, 2, 4, 6 and 8 weeks old, were sacrificed. 125I-labeled gentamicin uptake was measured in renal cortical slices as the cpm/mg wet tissue slice/medium (S/M) ratio. There was a significant age-related increment in gentamicin uptake. S/M ratios at 2, 4, 6 and 8 weeks were 3.49 +/- 0.46 (n = 7), 3.52 +/- 0.37 (n = 10), 4.23 +/- 0.42 (n = 10), 4.81 +/- 0.45 (n = 17), respectively (mean +/- SD; r = 0.78; p less than 0.01). Intraperitoneal injections of gentamicin were administered to another group of rats for 10 consecutive days from age 2 weeks and more. Gentamicin uptake of their renal cortical slices at 6 weeks of age was similar to that observed in the parallel age group of the nonstimulated rats (S/M ratio 4.18 +/- 0.41).