We conducted a prospective, double-blind, randomized trial of gentamicin and tobramycin to evaluate differences in nephrotoxicity. We evaluated levels of creatinine, creatinine clearance, beta 2-microglobulin, and N-acetyl-beta-D-glucosaminidase (NAG) as indicators of nephrotoxicity, and attempted to correlate them. Forty patients met the criteria for evaluation; 14 were given tobramycin and the remaining 26 received gentamicin. Significant nephrotoxicity, as defined by an increase in creatinine of 0.5 mg/dL, did not occur in either group. Increases in beta 2-microglobulin values were seen in 67% of the patients in the tobramycin group, and 52% of those in the gentamicin group. Elevations in NAG levels occurred in 54% of those in the tobramycin group and 52% of those in the gentamicin group. Elevation of NAG and beta 2-microglobulin levels was congruent in only 40% of the cases. We conclude that there was no significant difference in nephrotoxicity between gentamicin and tobramycin. Elevations of NAG and beta 2-microglobulin occurred at rates similar to those reported in the literature, but they did not correlate with significant nephrotoxicity.