Microspherocytes, measuring 2-3 mum in diameter, and cells with blunted projections or triangular in shape characterized the erythrocoyte morphology in three children with congenital haemolytic anaemia. Since the erythrocyte morphology resembled that associated with thermal injury, heat-induced changes in erythrocyte morphology and membrane composition were studied. Erythrocytes developed filaments and spheroid bodies which fragmented, resulting in microspherocyte transformation. Normal cells required exposure to 49 degrees C, whereas the patients' cells fragmented at 45 degrees C. Fragmentation was also observed during incubation of patients' cells at 37 degrees C for 17h. The heat-induced transformation of the patients' cells was associated with an increase in the membrane cholesterol:phospholipid and cholesterol:protein ratios. The phospholipid:protein ratio was unchanged. This suggests that fragmentation produces a selective loss of membrane components. Splenectomy ameliorated the haemolytic process. We propose that the patients' red-cell morphology is the result of in vivo fragmentation, and that the spleen is the major site of microspherocyte and poikilocyte destruction.