Ten patients with a mean age of 34.1 years with infective endocarditis (55% of cases due to Staphylococcus aureus) were treated with cephradine. The peak serum levels of cephradine (8–42 μg/ml) were 3− to 17-fold higher than the minimum inhibitory concentrations of cephradine against pathogenic strains of S aureus (1.2–4 μg/ml). Patients treated with cephradine became afebrile in 2 to 13 days of therapy, and their white blood cell count returned to a normal level in 3 to 30 days. Cephradine therapy was well tolerated without any incidence of phlebitis. The drug could be administered by three different routes. Cephradine is a useful cephalosporin for treatment of nonenterococcal gram-positive endocarditis in young heroin addicts.