An outbreak of staphylococcal infections of infants and nursing mothers and the resultant epidemiologic investigation are described. Accepted methods of routine prophylaxis of skin infection in the newborn nursery are re-evaluated. Control of the epidemic was quickly achieved through the routine prophylactic administration of erythromycin to all infants in the nursery. No erythromycin-resistant strains of coagulase-positive staphylococci emerged as the result of this method of epidemic control. There were no untoward reactions to the antibiotic among 463 infants who received erythromycin prophylaxis.