The effects of ethanol on phosphorylation in the erythrocyte ghost membranes was studied. Four groups of rats were used: controls; prodromal phase; overt withdrawal syndrome; and treated with a single dose (6g/kg) of ethanol. Spectrin (Band 2) phosphorylation was enhanced during prodromal phase (200 +/- 12%) and during overt ethanol withdrawal syndrome (150 +/- 18%), while a single dose of ethanol produced no significant change. Addition of micromolar calcium chloride solution to the phosphorylating medium produced pronounced decrease in spectrin phosphorylation in the ghost membranes isolated from controls and those treated with a single dose of ethanol, while this effect of calcium was less pronounced in the ghost membranes isolated from rats in the prodromal phase and in the withdrawal syndrome. This suggests that due to prolonged ethanol treatment membrane phosphorylating properties were less sensitive to the change in calcium concentration. The membrane polypeptide composition was unaffected upon ethanol treatment.