Bacterial brain abscesses occur in approximately 1500 to 2500 patients each year in the United States. Multiple abscesses have been noted in 10 to 50% of these patients. The goal of this study was to better define the roles of surgery and medical management in patients harboring multiple brain abscesses and to develop an algorithmic approach to the treatment of these complex patients. Between 1976 and 1992, 16 patients with multiple brain abscesses were treated by a single physician (M.L.R.). The ages of the patients ranged from 1.5 to 73 years (median, 47 yr). In all patients, a diagnosis of multiple abscesses was made by computed tomography (15 patients) or magnetic resonance imaging (1 patient) brain scans. The number of abscesses per patient ranged from 2 to 30, and the abscesses were located in all regions of the brain. Thirteen received a combination of antibiotics and surgical drainage, and three received antibiotics only. Surgery was performed on abscesses larger than 2.5 cm or on those situated in critical areas of the brain or causing significant mass effect. Excision and open aspiration via craniotomy and stereotactic aspiration were analyzed on the basis of the location of the lesion and infecting organism. Any abscess that enlarged after 2 weeks of antibiotics or that failed to shrink after 3 to 4 weeks of antibiotics was again aspirated or excised. Forty-three surgical procedures were performed in 13 patients, and 8 (62%) of the patients operated on required more than one surgical procedure. No significant morbidity was observed in any of the surgical procedures. Antibiotics were administered intravenously for an average of 6 to 8 weeks and were adjusted according to organism type and sensitivity to antibiotics. One patient (6%) died, and the remaining 15 patients had resolution of all abscesses and good neurological recovery within 6 months. On the basis of these results, we propose a combined surgical and medical approach to the treatment of patients with multiple brain abscesses. We recommend the aggressive surgical drainage of all abscesses larger than 2.5 cm in diameter, combined with 6 to 8 weeks of intravenous antibiotics. Biweekly computed tomography or magnetic resonance imaging is necessary to closely monitor patients for evidence of abscess growth or failure to resolve despite antibiotics, prompting another operation. The application of this combined approach should yield cure rates of more than 90% in patients with multiple brain abscesses, a result similar to that expected when treating patients with solitary lesions.