To compare the efficacy of dopamine and dobutamine for the treatment of hypotension (mean arterial blood pressure, < or = 30 mm Hg) in preterm (< or = 34 weeks of gestation) infants with respiratory distress syndrome in the first 24 hours of life, we enrolled 63 hypotensive preterm infants in a randomized, blind trial. Inclusion criteria required an arterial catheter for measurement of mean arterial blood pressure, treatment with exogenous surfactant, and persistent hypotension after volume expansion with 20 ml/kg (packed erythrocytes if hematocrit < 0.40, 5% albumin if > or = 0.40). Intravenous study drug infusions were initiated at 5 micrograms/kg per minute and then increased in increments of 5 micrograms/kg per minute at 20-minute intervals until a mean arterial blood pressure > 30 mm Hg was attained and sustained for > or = 30 minutes (success) or a maximum rate of 20 micrograms/kg per minute was reached without resolution of hypotension (failure). The study groups at entry were comparable for birth weight, gestational age, postnatal age, gender, birth depression, hematocrit < 0.40, heart rate, oxygenation index, delivery route, maternal chorioamnionitis, and maternal magnesium or ritodrine therapy. No infants in the dopamine group had a treatment failure (0/31; 0%); (16%) of 32 infants failed to respond to dobutamine (p = 0.028). Success was attained at < or = 10 micrograms/kg per minute in 30 (97%) of 31 infants given dopamine and in 22 (69%) of 32 infants given dobutamine (p < 0.01). Among those treated successfully, the increase in mean arterial blood pressure was significantly higher in those given dopamine (mean, 11.3 vs 6.8 mm Hg; p = 0.003). We conclude that dopamine is more effective than dobutamine for the early treatment of hypotension in preterm infants with respiratory distress syndrome.