Thirty-three patients with viridans streptococcal infective endocarditis were treated for two weeks with intramuscular procaine pencillin, 1.2 million units every 6 hours, plus streptomycin, 500 mg intramuscularly every 12 hours. Nine patients (27%) had infections with relatively penicillin-resistant microorganisms (MIC greater than 0.1 microgram/ml or MBC greater than or equal 3.12 microgram/ml). Follow-up ranged from 2 months to 3.5 years. There were no relapses; Mild vestibular toxicity developed in one patient. One patient died two months after completion of antimicrobial therapy from sudden onset of severe congestive heart failure; Seven patients required cardiac valve replacement after completion of antimicrobial therapy. None died. We believe that this therapeutic regimen is effective antimicrobial therapy for infective endocarditis caused by viridans streptococci, irrespective of in vitro microbiologic data.