Published reports suggest a gender-related difference in susceptibility to the nephrotoxicity of gentamicin which may also be strain-related in rats. However, certain ambiguities exist in the results obtained with the functional and morphologic determinants of nephrotoxicity used in these studies. Within the same experimental protocol we examined the potential gender-related differences in tobramycin nephrotoxicity in age-matched male and female rats of both the Sprague-Dawley (SD) and Fischer (F344) strains. Equal numbers of both genders were dosed at 30 mg/kg (F344) and 90 mg/kg (SD) twice daily for 9 days. Results of BUN, serum creatinine, whole body weight change and histologic score comparisons (P < 0.05) indicate that male F344 rats are more sensitive to tobramycin nephrotoxicity than F344 females but this gender-related susceptibility was not observed in SD rats.