Phagocytic and bactericidal functions of polymorphonuclear leukocytes and the development of serum opsonic activity in newborn infants were studied using Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa as the test organisms. Ingestion and intracellular killing of the bacteria were normal in leukocytes from 18 infants as was the reduction of nitro blue tetrazolium by phagocytizing leukocytes from 41 infants. Opsonic activity for the three bacteria was deficient in infants under 3,000 gm (6 lb 10 oz) with 10% and 2.5% concentrations of cord sera. Seventy-five percent to 100% of the opsonic activity of cord sera was heat-labile. Total hemolytic complement activity and the third component of complement (C′3) were measured and found to be related to birth weight. A significant relationship between C′3 levels and opsonic activity for S aureus and P aeruginosa was observed.