A retrospective study of patients who received chloramphenicol for the treatment of serious vancomycin-resistant enterococcal infections between 1 January 1993 and 31 August 1993 was conducted at the University of Pennsylvania Medical Center (Philadelphia). Antimicrobial susceptibilities as well as the clinical course of infection, adverse events, and response to therapy of 16 patients were reviewed. Forty-seven percent of enterococcal isolates were susceptible only to chloramphenicol, tetracycline, and nitrofurantoin. Types of infection included bacteremias (n = 7), abscesses (n = 7), and others (n = 5). Of 14 patients for whom a clinical response could be ascertained, eight (57%) showed improvement after treatment. Of 11 patients for whom a microbiological response could be ascertained, eight (73%) had sterile cultures after treatment. No lasting adverse effect related to the drug occurred. In-hospital mortality was 56%, but only one death could be directly attributed to vancomycin-resistant enterococcal infection. Chloramphenicol appears to be a useful and well-tolerated agent for the treatment of serious vancomycin-resistant enterococcal infections.