Exposure of human erythrocytes to ethanol (1 to 20% by vol) in Ca2+ and Mg2+-free phosphate-buffered saline, pH 7.4, transformed biconcave discs into spiculated echinocytes within 3 min at 25 degrees C. The effects of ethanol were concentration-and time-dependent, but reversible by washing in the incubation buffer system within 60 min of initial exposure to ethanol. After prolonged ethanol exposure (180 min), washing of cells resulted in the formation of stomatocytes (cup-forms). Ethanol-induced echinocytosis was also accompanied by a 30% enhancement in the agglutinability of erythrocytes by ligands with high affinity for negative surface charge (poly-L-lysine and wheat germ agglutinin, 20 microliters/ml) without any alterations in surface charge topography. Concomitant exposure of erythrocytes to prostaglandin E1 (100 nM) selectively prevented the enhancement of ligand-mediated agglutinability, but did not modify cell shape. These data indicate that certain erythrocyte surface properties may not be directly influenced by cell shape and suggest a unique modulatory action of prostaglandin E1 on shape-transformed cells.