Correct analysis of whole blood volatile organic compounds (VOCs) in evaluating possible exposure situations requires differentiation of smokers from nonsmokers. Whole blood concentrations of 2,5-dimethylfuran are determined using an internal standard method, and the concentrations of this compound are evaluated as a marker for smoking in exposure-study subjects. Results indicate that the concentration of 2,5-dimethylfuran can be adequately determined in whole blood by a method already in use for determining VOCs in blood. The whole blood concentration of 2,5-dimethylfuran was an excellent predictor of smoking when compared with positive responses about smoking on questionnaires. Using a detection limit of 0.024 ppb, 2,5-dimethylfuran concentrations in blood correctly identified the smoking status of 96.4% of the subjects in this study. The blood 2,5-dimethylfuran concentration was linearly related to the number of cigarettes smoked per day. This method is advantageous since blood 2,5-dimethylfuran concentrations can be determined using the same method used to determine concentrations of other VOCs, thus obviating the need for additional analytical procedures.