Anemia develops in about a fourth of women whose pregnancy is complicated by pyelonephritis, although its exact mechanism has not been defined clearly. In this study of 18 women with antepartum pyelonephritis, although only a third had anemia (hematocrit less than 30 vol/dl), there was evidence for hemolysis in all 18. Specifically there was a mean decrease in hematocrit of 5 vol/dl from admission to discharge. With scanning electron microscopy, we compared erythrocyte morphologic aberrations that were found in women with renal infection with those of normally pregnant women, and the former had significantly increased proportions of echinocytes in particular, but schistocytes and spherocytes were increased also (total 10.3% vs 1.4%, p less than 0.0001). These changes, especially echinocytosis, have been induced in vitro by lipopolysaccharide, and they are known to lead to premature red blood cell destruction in vivo. We conclude that hemolysis with subsequent anemia in pregnant women with pyelonephritis is caused by lipopolysaccharide-induced red blood cell membrane damage.