Ninety percent of the 49 reported cases of serious Erysipelothrix rhusiopathiae infection have been episodes of presumed or proved endocarditis. E. rhusiopathiae endocarditis correlates highly with occupation (farming, animal exposure), affects more males than females, exhibits a peculiar aortic valve tropism, displays a characteristic erysipeloid cutaneous lesion (in 40% of cases), and is associated with significant mortality (overall rate, 38%). Comparison with other unusual gram-positive rods causing endocarditis shows that E. rhusiopathiae resembles Listeria monocytogenes and Lactobacillus species in its propensity to involve structurally damaged but native left-sided valves. Unlike diphtheroid endocarditis, E. rhusiopathiae endocarditis has not involved prosthetic valves and is not associated with intravenous drug abuse, as is Bacillus species endocarditis. E. rhusiopathiae is exquisitely susceptible to penicillin but resistant to vancomycin. Since vancomycin is often employed in empiric therapy for presumed endocarditis, prompt microbiologic differentiation of E. rhusiopathiae from other gram-positive organisms is necessary to avoid delays in the initiation of appropriate antibiotic therapy.