Group G streptococci were isolated from various clinical sites in 64 patients hospitalized between 1979 and 1983. Oropharyngeal and wound infections occurred most commonly, although some of these isolates represented colonization. Ten patients had serious infections including five with endocarditis. Patients with endocarditis tended to be older, had underlying conditions predisposing them to infection, and responded poorly to single agent therapy with penicillin G or other beta-lactam agents, despite exquisite in vitro susceptibility. Patients with serious infections but without endocarditis tended to be younger, had fewer underlying disorders and responded rapidly to therapy with beta-lactam antibiotics. All isolates were susceptible to penicillin G, cephalothin, vancomycin and newer beta-lactam agents. Occasional tolerance was observed. Combinations of penicillin G with an aminoglycoside and of vancomycin with an aminoglycoside or rifampin were bactericidal against the tolerant strains. Although none of the organisms isolated from patients with endocarditis were tolerant, this infection should be treated with combination antibiotic therapy.