Sixty-nine hospitalized patients with serious systemic infections, mainly surgical wound infections, soft-tissue abscesses, peritonitis, or pneumonia, were treated either with sisomicin or gentamicin by parenteral administration for periods ranging from 5 to 14 days. In general, sisomicin-treated patients received a mean daily dosage of 2.6 to 3.9 mg/kg and gentamicin-treated patients 3.0 to 5.1 mg/kg. The results, based on the combined clinical and bacteriological responses, showed an overall cure rate of 74% for the 34 patients on sisomicin compared with 37% of the 30 patients on gentamicin for whom a definite evaluation could be made. This difference was statistically significant (p = 0.005). The bacteriological findings also suggest that sisomicin was more effective than gentamicin in eliminating Pseudomonas aeruginosa from infected patients. Local tolerance was good to both drugs. A change in auditory function was reported in 1 patient on gentamicin. Mild changes in renal function, possibly drug related, were recorded in 5 patients (1 on sisomicin and 4 on gentamicin).