From 1970 to 1983, five patients with group B streptococcal endocarditis were treated at the Mayo Clinic, Rochester, Minn. The minimal inhibitory concentration and the minimal bactericidal concentration of penicillin were 0.09 microgram/mL or less and 1.56 micrograms/mL or less, respectively. The in vitro activity of cefazolin against group B streptococci was similar to that of penicillin. In three of the five cases, penicillin and streptomycin acted synergistically in vitro against group B streptococci. Four of the five patients were cured, three by use of an aminoglycoside combined with penicillin, ampicillin, or vancomycin. Three of the five patients had multiple large systemic emboli, and one of the three died of brain-stem infarct. Penicillin alone or in combination with an aminoglycoside is effective therapy for group B streptococcal endocarditis. Patients unable to tolerate penicillin may be treated with cefazolin or vancomycin. Clindamycin therapy should be avoided in patients with endocarditis caused by strains that are tolerant in vitro to clindamycin.