Zieve's syndrome (ZS), which consists of transient haemolytic anaemia, jaundice, hyperlipoproteinaemia, and alcohol-induced liver disease, was studied in male patients during the acute (n = 20) and the remittent (n = 10) phase. Chronic alcoholics (n = 10) without haemolysis and healthy male persons (n = 10) served as controls. Erythrocytes were separated into old and young cells by means of density-layer centrifugation. Those fractions which contained older red cells disclosed a pyruvate-kinase instability which resulted in impaired metabolism. Changes in membrane lipid composition as indicated by increased cholesterol and polyunsaturated fatty acids (PUFA) were also detected in patients during the acute phase of ZS. Alcohol-induced red-cell vitamin-E deficiency with a decrease in PUFA levels may provoke an oxidation of reduced red-cell glutathione which in turn results in the enzyme instability. This study lends further support to the hypothesis that the putative role of the red-cell metabolic injury in the origin of haemolysis in ZS cannot be envisaged without introducing membrane-linked and extracellular cofactors.