Because of the anecdotal but unconfirmed inferences of the greater sensitivity of Fischer rats to aminoglycoside nephrotoxicity, an intrastudy comparison of the sensitivity of Fischer and Sprague-Dawley rats to aminoglycoside nephrotoxicity was undertaken. Tobramycin was administered at 3 dose levels to each strain of rat for 10 days. Nephrotoxicity was evaluated utilizing a spectrum of both functional and morphologic assessments of renal proximal tubular integrity. The results confirm that the aged matched Fischer rat is more sensitive to the nephrotoxic effect of tobramycin than the Sprague-Dawley. These results also suggest an opportunity to study quantitative and perhaps qualitative differences in pathogenic mechanisms of aminoglycoside nephrotoxicity in a single laboratory animal species.