Forty-eight patients with 51 episodes of infective endocarditis caused by streptococci were studied in a comparison of the efficacy of single antibiotic therapy versus that of combination therapy. There was no statistical difference in terms of clinical course, toxicity, and mortality between the group given a single drug and that given combination therapy. However, one patient experienced two relapses, in both instances after high-dose penicillin therapy. The species and antibiotic susceptibilities of the infecting organisms were determined. The majority of isolates were alpha-hemolytic, with Streptococcus sanguis recovered most commonly. Streptococcus bovis and group B beta-hemolytic streptococci were the next most frequent isolates.