Bacterial plasmids have become valuable markers for the comparison of strains of nosocomial gram-negative bacilli. The importance of plasmids in nosocomial infections is primarily due to their transferable antibiotic resistance genes (R plasmids), but other plasmid-mediated traits may eventually serve as potential markers. Stable cryptic plasmids have also served to relate outbreak strains, particularly nonfermenting strains of gram-negative bacteria. Klebsiella pneumoniae and Serratia marcescens have been the major plasmid-containing species in outbreaks involving single or multiple species. Outbreaks of single species with common plasmid patterns have included the Enterobacteriaceae, Pseudomonas aeruginosa, Pseudomonas cepacia, Ewingella americana, and Legionella pneumophila. Intrageneric spread of the same or similar R plasmids has nearly always occurred within the Enterobacteriaceae in large medical centers or Veterans Administration hospitals. High-risk nurseries and burn units have been conspicuous foci for R plasmid evolution. Hospital epidemiologists and clinical microbiologists will likeiy have an ever-increasing need to determine the plasmid content of gram-negative bacilli producing endemic and epidemic nosocomial infections.