The adenine nucleotides present in distinct cellular compartments of platelets of 27 patients affected with essential thrombocythemia have been measured. In order to quantify granule-bound nucleotides and adenylic cytoplasmic pool, platelets have been stimulated with thrombin or treated with increasing digitonin concentrations, respectively. Among patients, we have identified two groups: 12 patients (Group 1) had normal platelet level of ATP and ADP both in dense granules as well as in cytoplasmic pool. The other patients (Group 2) had granule ATP and ADP significantly lower and ATP/ADP ratio significantly higher than controls. In these patients an increase in hypoxanthine level, derived from metabolic ATP degradation occurring during stimulation, was observed. In addition, in the latter patients an increased resistance of plasma membrane to digitonin was shown, suggesting that membrane fluidity should be reduced owing to a modified cholesterol/phospholipid ratio.