The purpose of this study was to determine the safety and efficacy of home intravenous antibiotic therapy in treating secondary bacterial infections in patients infected with the human immunodeficiency virus (HIV). This study was a subset analysis of 22 patients with HIV, enrolled in two centers of a multicenter, open-label, prospective study. When necessary, patients were stabilized as inpatients, followed by home therapy. Enrolled patients had diagnoses of pneumonia, skin and soft-tissue infections, bacteremia/septicemia, or other infections requiring parenteral therapy. A third-generation cephalosporin, cefotaxime, 1-2 g every 8 hours, was delivered intravenously using an ambulatory delivery system (ADS). Home therapy with cefotaxime/ADS produced a clinical response rate of 95% and bacteriologic response of 88.2%. The requirement for and duration of inpatient therapy was markedly reduced compared with diagnosis-related group (DRG) allotments. In conclusion, home intravenous antibiotic therapy with cefotaxime in patients infected with HIV is effective and safe. It may improve quality of life by reducing the length of hospital stay.