Phosphatidylethanol (PEth) is an abnormal phospholipid which is formed in the presence of ethanol, via the action of phospholipase D (PLD). PEth in blood is a potential marker of alcohol abuse. The present study was made to determine the compartmentalization and the elimination rate of PEth in human whole blood. PEth was assayed by an improved HPLC technique, with evaporative light-scattering detection. Blood from six alcoholic males was separated into different blood cell fractions. The PEth concentration in whole blood was 2.5+/-0.9 and 1.9+/-1.1 micromol/l in erythrocytes. Only one subject had detectable PEth in the mononuclear cells. Fifteen patients (13 men, two women) with chronic alcoholism, were followed as inpatients, after admission to an alcohol detoxification clinic. PEth, carbohydrate-deficient transferrin (CDT) and gamma-glutamyltransferase (GGT) were measured on days 1, 3, 5 and 7 after admission. Linear regression analysis of logarithmic PEth values in individuals, with measurable PEth at day 1, gave a good fit (P<0.001) with the one-compartment elimination model. The half-life was calculated as 4.0+/-0.7 days. A weak significance (P<0.05) was observed in the correlation of PEth at day 1 and half-life values of the same subjects.