During an outbreak, 25 severely impaired patients (mean age 62) presented with severe infections due to Staphylococcus aureus resistant to oxacillin and aminoglycosides. All strains were isolated in pure culture and diagnostic procedures included transtracheal puncture and bone biopsy. Median MICs were: oxacillin 50 mg/l, gentamicin 12.5 mg/l, tetracycline 25 gm/l, vancomycin 0.195 mg/l, rifampicin 0.097 mg/l and minocycline 0.195 mg/l. All patients were treated with rifampicin (600 mg/day) and minocycline (200 mg or 400 mg/day) administered together intravenously or orally bid. Mean duration of treatment was 22 days (range 5 to 119). Overall results were 19/25 infections cured and one improved. Five were failures due mostly to emergence of Staph. aureus resistant to rifampicin. No side effects were noted. These preliminary results suggest that rifampicin plus minocycline may be useful in the treatment of severe infections due to multi-resistant Staph. aureus.