In April 1978, a strain of gentamicin-resistant Klebsiella pneumoniae (GRK) was introduced into the neonatal intensive care unit of Henry Ford Hospital. An additional ten cases of GRK occurred over the subsequent 16 months and intestinal colonization occurred in up to 91% of admissions per month. All GRK were susceptible to amikacin and were capsular serotype 19. Though hand contamination of hospital personnel with GRK was documented, increased handwashing practices did not reduce colonization rates of neonates with the epidemic strain. Intestinal carriage persisted for up to ten months and could not be eradicated by administering oral colistin sulfate. Discontinuation of gentamicin and utilization of amikacin were associated with a significant reduction in colonization with GRK (p < 0.05). However, the only control measure that prevented both new cases and colonization with the epidemic strain was the utilization of a strict cohort system.