Evaluation of 612 episodes of gram-negative bacteremia over a 10-year period demonstrated its progressively increasing frequency. This increase was associated with an increasing proportion of patients with more severe underlying disease, increasing patient age, increasing frequency of cardiac surgery and manipulative procedures, and increasing frequency of treatment with antibiotics, corticosteroids and antimetabolites in patients with bacteremia. Fatality rates paralleled the severity of the host's underlying disease as noted in previous reports. The urinary tract was the most frequent source of bacteremia, but in 30 per cent of the patients, predominantly those with more severe underlying disease, the original source could not be identified. Of all blood cultures obtained in these patients, 72 per cent were positive. Bacteremia was of low magnitude with 77 per cent of the patients have quantitative blood cultures with less than 10 gram-negative bacilli per milliliter of blood. Escherichia coli was the most frequent etiologic agent followed in frequency by Klebsiella-Enterobacter-Serratia species, Pseudomonas aeruginosa, Proteus and Providencia species, and species of Bacteroides. Sixteen per cent of the bacteremias were polymicrobic. K and O-antigen typing of Escherichia coli and capsular typing of K. pneumoniae demonstrated that a large number of serologic types of these strains were responsible for bacteremia. Over-all, bacteremia caused by multiple species of bacteria was associated with higher fatality rates, but no significant differences in fatality rates could be demonstrated for bacteremias caused by individual species of gram-negative bacilli when comparisons were made between patients with underlying diseases of similar severity. The presence or type of K-antigen did not influence the lethality of Esch. coli infections. Although some O-antigen types, 0:4, 0:6 and 0:8, were associated with higher fatality rates than other O-antigen types, "rough" or autoagglutinable Esch. coli were as lethal as smooth strains. These findings indicate that bacterial factors, other than antibiotic resistance, have little influence on the outcome of gram-negative bacteremia and that gram-negative bacilli function primarily as "opportunistic" pathogens.