Red blood cell osmotic fragility and autohemolysis studies were performed on 35 patients with aortic ball-valve prostheses. Osmotic fragility on fresh heparinized blood was normal. After 24 hours' incubation, it was increased in 17 patients. The most common abnormality was a "tail" of cells with increased fragility indicative of a heterogeneous population of cells. Sixteen patients with increased fragility had cloth-covered Starr-Edwards prostheses; the majority had intravascular hemolysis. Nine patients with normal fragility had Cutter or Magovern prostheses; the majority had minimal hemolysis. Autohemolysis after 48 hours' incubation with glucose was normal in all patients. Increased incubated osmotic fragility frequently reflects damage to red blood cells by prosthetic heart valves, and increased osmotic fragility is often associated with increased rates of hemolysis in vivo. The damage is greater with cloth-covered Starr-Edwards than with Magovern or Cutter prostheses.