Two separate outbreaks due to Flavobacterium meningosepticum type E occurred in a neonatal intensive care unit in March-April and July 1975. The first outbreak involved all five infants in the unit. Two infants developed meningitis, one had bacteremia, and two were colonized. During the second outbreak, five of seven infants were colonized but none developed disease. The upper respiratory tract was colonized first in most instances, and the organism persisted at this site for a mean of 17.3 days. Duration of colonization was more prolonged in infants receiving antibiotics than in untreated infants. Extensive environmental surveillance failed to demonstrate a reservoir, however, F. meningosepticum was recovered from three nasoendotracheal tubes and from an aerosol tube before colonization of four infants. The organism was resistant to most antimicrobial colonization of four infants. The organism was resistant to most antimicrobial agents tested and developed resistance to others during the treatment course of one infant. Although F. meningosepticum was not recovered from cultures of transport vehicles, several other gram-negative bacteria were isolated and were also resistant to multiple antibiotics.