The aim of our prospective clinical study was to determine whether the combination of tobramycin plus cefotaxime is more nephrotoxic than tobramycin alone. The studies were carried out in 30 patients with serious infections and normal renal function. Groups of ten patients each received either 2 g cefotaxime or 1 mg/kg body weight tobramycin or cefotaxime and tobramycin in the same dosage every eight hours intravenously for at least seven days. Serum creatinine, creatinine clearance and alanine aminopeptidase (AAP) excretion in 24-hour urine were determined before, during and five days after the antibiotics had been discontinued. These were used as parameters for glomerulotubular injury. The plasma levels of tobramycin and cefotaxime (assayed by agar diffusion) did not differ when the drugs were given alone or in combination. None of the patients treated with cefotaxime alone showed any signs of renal damage. In contrast, tobramycin alone or in combination with cefotaxime caused an increase in urinary enzymes in all patients. This activity was a mean five to six times greater than the initial values prior to antibiotic therapy. There were no significant differences between the AAP increase during treatment with tobramycin and tobramycin plus cefotaxime. Four to five days after discontinuing antibiotic therapy, AAP activity decreased to values similar to those measured prior to therapy. In some of the patients receiving tobramycin alone or in combination with cefotaxime, increased creatinine levels, a reduction in creatinine clearance to 60 ml/min and an increase in renal enzyme excretion could be observed. Thus, treatment with high doses of cefotaxime does not seem to increase tobramycin nephrotoxicity in patients with normal renal function. The nephrotoxicity of this drug combination is obviously due to the aminoglycoside.