Twenty-eight strains of E. coli isolated from infants were compared with respect to opsonic requirements, sensitivity to serum, and ability to activate serum chemotactic factors. Six of the strains were isolated from stools of healthy newborn infants; 22 were isolated from the cerebrospinal fluid or blood of infants with meningitis and/or septicemia. Eighteen of the strains had K1 polysaccharide antigen. Fourteen of the strains (seven with K1 antigen) activated complement via the alternative pathway and all of these strains were well opsonized in 4% pooled human serum. A higher concentration of serum was necessary to opsonize 12 of the 14 strains that did not activate the alternative pathway. A wide variation was also found in opsonic requirements of E. coli strains isolated from healthy and sick infants. There was no relationship of the K1 antigen to opsonic requirements, to capacity to activate complement via the alternative pathway, to generation of chemotactic factors, or to sensitivity to serum cidal activity. Therefore, the association of E. coli with K1 antigen and neonatal meningitis did not appear to be related to these bacteria-serum interactions.