At the Mayo Clinic, 56 patients with infective endocarditis caused by gram-negative bacteria were seen from 1958 through 1979, 35 of whom were seen from 1970 through 1979. The patients were categorized into two divisions: those with medical, naturally acquired valve infections (40 [71%]) and those with infective endocarditis after cardiac operation (16 [29%]). The overall cure rate was 82% (46 of 56 patients); 35 of 40 patients (88%) were cured in the medical group, and 11 of 16 patients (69%) were cured in the surgical group. The patients were further classified on the basis of organism: group 1 (33 patients)--infections caused by Haemophilus (18), Actinobacillus actinomycetemcomitans (4), Cardiobacterium hominis (6), Eikenella corrodens (2), Kingella kingii (2), and Bordetella bronchiseptica (1); 32 of these 33 patients (97%) were cured, and 6 of these infections were on prosthetic valves; group 2 (21 patients)--infections caused by enteric aerobic bacilli; 13 of the 21 patients (62%) were cured; group 3 (1 patient)--infection caused by anaerobes (Bacteroides fragilis); this patient died; and group 4 (1 patient)--infection caused by Neisseria gonorrhoeae; this patient was cured. The gram-negative bacteria in the survivors and nonsurvivors and the curative antibiotic regimens were tabulated. Among the 35 survivors in the medical group, a combined antibiotic regimen cured 21 patients (60%) and a single antibiotic agent cured 14 (40%). Among the 11 survivors in the surgical group, combined therapy was given to 8 (73%), a single drug was used once, and operation alone achieved a cure in 2 patients. Compared with past data, the current study indicates an increasing incidence of gram-negative bacterial endocarditis (approximately 10%) and an improving cure rate 82%).