Shape, volume and protein phosphorylation of RBC were studied in normal subjects and patients with essential hypertension. Mean volume of RBC of hypertensive patients was reduced by 3-4%, as compared to the control group. The level of band 4.9 phosphorylation was simultaneously increased in RBC of hypertensive patients. Activation of protein kinase C with phorbol ester produced volume reduction and shape changes in RBC. These changes are accompanied with phosphorylation of bands 4.1 and 4.9. It is suggested that RBC volume reduction in essential hypertension may be related to an alteration in the regulation of cytoskeleton proteins phosphorylation.