There were 4 patients with infective endocarditis caused by A. actinomycetemcomitans reported. The clinical course was characterized by chronicity. Three of the 4 patients were treated with combined penicillin and aminoglycoside therapy on an empiric basis; the 4th patient was given ampicillin alone for 3 wk. Cure was achieved in all 4 cases, with antibiotic therapy alone in the first 3 and ampicillin alone plus valve replacement surgery in the 4th patient. Further in vitro bactericidal data are needed, and actual therapy with ampicillin alone is desirable to see whether these patients with endocarditis of natural valves cannot be treated with ampicillin alone for 3 wk.