In a prospective study, 91 patients with penicillin-sensitive infective endocarditis (IE) were treated for two weeks with intramuscular (IM) penicillin G procaine, 1.2 million units every six hours, plus streptomycin sulfate, 500 mg IM every 12 hours. Viridans streptococci were isolated from 70 patients (77%); 21 patients (23%) had Streptococcus bovis infections. Eighteen patients (20%) had had symptoms of IE for three months or longer. Follow-up ranged from two months to 6.6 years. There were no relapses; mild vestibular toxic reactions occurred in two patients (2%). Two patients (2%) died--one of sudden-onset severe heart failure and one of cardiac arrest after aortic valve replacement. Twenty-six patients (19%) required cardiac valve replacement after completion of antimicrobial therapy. This therapy seems as efficacious as four weeks of parenteral antimicrobial therapy and is more cost-effective.