We have sought to elucidate the spiculated shape of McLeod erythrocytes. Red cells from a normal donor and from a McLeod patient were incubated in phosphate-buffered saline containing 0, 0.05, or 0.1 mM chlorpromazine at 0 degrees C for 5 min, then glutaraldehyde-fixed, and examined by scanning electron microscopy. The normal red cells were biconcave disks in which chlorpromazine induced inward (negative) curvature: deep cupping (stomatocytosis) and multiple invaginations. The McLeod cells were mostly spiculated. Chlorpromazine at lower concentration converted them into biconcave disks and, at higher concentration, into stomatocytes. These results support the hypothesis that the spiculation of McLeod cells is the result of an imbalance of surface area between the two lipid leaflets of the membrane; that is, a bilayer couple effect. We determined the numerical density of intramembrane particles (IMP) in replicas of both fracture faces of red cells subjected to freeze fracture and rotary shadowing. These values were as follows (expressed per microns 2 of membrane +/- SD): the normal protoplasmic fracture face had 2200 +/- 306 and the McLeod had 2300 +/- 250. The normal exoplasmic fracture face had 388 +/- 75 and the McLeod had 330 +/- 59. We conclude that there is no evidence for derangement of band 3, the principal protein in the IMP, in McLeod erythrocytes.