Patients with serious infections often remain hospitalized solely to continue parenteral antibiotic therapy although many who are afebrile and medically stable could complete treatment in an outpatient setting. Potential advantages of outpatient treatment include lower costs and greater efficiency in the use of hospital beds, and economic and psychological benefits to patients. Cefonicid, a parenteral cephalosporin with an extended antibacterial spectrum and a prolonged serum half-life, was used to treat 39 patients with serious infections, mostly those of bone or soft tissues. Staphylococcus aureus was the predominant pathogen isolated (18 patients); nine gram-negative aerobes were observed in single instances. After indicated surgical procedures and inpatient intravenous antibiotic therapy, the patients were discharged to continue parenteral therapy at home with once-daily intramuscular doses of cefonicid. Mean duration of outpatient therapy was 16 days. The clinical response was satisfactory in all but two patients, one with relapse of a S aureus wound infection, the second with a gram-negative reinfection at the site of a bone cyst. Systemic and local tolerability of cefonicid were good. It is concluded that outpatient antibiotic therapy with intramuscular cefonicid can benefit both patients and hospitals.