We report our experience with linezolid in an investigation of its use against resistant grampositive bacterial infections. Fifteen patients who had renal failure (n = 6), recent liver transplantation (n = 5) or surgery (n = 6), cancer (n = 3), endocarditis (n = 2), or human immunodeficiency virus infection (n = 1), along with infections due to vancomycin-resistant enterococcus (VRE), and 2 patients with infections due to methicillin-resistant Staphylococcus species who had adverse reactions to vancomycin were treated with linezolid (600 mg every 12 h for 5-42 days (mean +/- SD, 20.5 +/- 3.5 days). Abscess drainage or prosthetic device removal was undertaken. Microbiological cure occurred in all 10 patients who completed therapy, and all 7 patients alive at follow-up were free of infection. No deaths were attributable to the index infection. Adverse events associated with linezolid use were mild leukopenia in 1 patient and nausea in another. It appears that administration of linezolid, in conjunction with surgical intervention or device removal, is an effective treatment option for serious resistant gram-positive bacterial infections.