Rats with polycythemia induced by exposures to simulated high altitudes developed a significantly higher incidence of endocarditis following intravenous bacterial injections than rats with cobalt polycythemia or ground level controls. No increase occurred in altitude rats when polycythemia was prevented by repeated bleedings. These findings suggest that both polycythemia and hypoxia are necessary to explain increased susceptibility of altitude rats. Cortisone increased susceptibility of ground level rats injected withStreptococcus faecalis. Unlike altitude exposures, however, cortisone did not render rats susceptible to endocarditis due toHemophilus parainfluenza.