Patients with gram-negative bacteremia studied between 1951–1958 (173 patients) and 1965–1974 (612 patients) were carefully evaluated to delineate critical determinants of outcome. Severity of the host's underlying disease was the major factor influencing outcome in both series. Early appropriate antibiotic therapy was associated with significant reductions in both fatality rates and the frequency of development of shock. Appropriate antibiotic therapy was also associated with a significant reduction in fatality rates even if initiated after the onset of shock. Most individual antimicrobial agents appeared to be of comparable efficacy provided the infecting organism was susceptible. Combinations of antibiotics could not be demonstrated to be more effective than single agents.