The safety and plasma concentrations of bovine superoxide dismutase (SOD), potentially useful in prevention of bronchopulmonary dysplasia, were evaluated in 19 prematures with severe IRDS. All were respirator dependent and required FiO2 greater than 0.7 at 24 h of age. Subcutaneous tests (0.1 mg/kg) and treatment doses (0.25 mg/kg) did not induce wheal and flare or systemic reactions. No abnormalities in serum electrolytes, calcium, glucose, creatinine concentrations, complete blood and platelet counts were noted. Following dose 1, SOD was detectable in all patients at 1 1/2 h and rose slowly to a peak at 4-8 h. Mean levels remained between 0.2 and 0.36 micrograms/ml during the 12-hour interval between doses. Similar responses resulted following doses 2-5 with mean levels between 0.36 and 0.68 micrograms/ml. SOD levels varied directly with serum creatinine levels obtained at the time of SOD administration but other factors such as skin perfusion were not controlled. The present study demonstrates that SOD at a dose of 0.25 mg/kg s.c. can be administered safely to prematures with severe IRDS and resulted in levels associated with therapeutic effects in adults.