The differential white blood cell (WBC) count often reveals relative lymphopenia in Cushing's syndrome and may be a clue to the discovery of the ailment. However, the incidence of this finding has rarely been reported in the literature. We conducted a study on 40 patients with Cushing's syndrome due to adrenocortical adenoma to evaluate the diagnostic implications of relative lymphopenia. Total WBC count, differential WBC count, basal level of plasma cortisol, urinary excretion of free cortisol and thyroid function were evaluated preoperatively. We also investigated the differential WBC count in 40 patients with thyroid tumors matched for age and sex with the Cushing's syndrome patients. The proportion of lymphocytes among WBCs was also compared between the two groups. The proportion of lymphocytes among WBCs was significantly lower in the patients with Cushing's syndrome (19.4 +/- 10.8%) than in those with thyroid tumors (42.3 +/- 9.5%, mean +/- SD, p < 0.05). The incidence of relative lymphopenia was high (82.5%) as well as that of increased urinary excretion of free cortisol (85.3%) in Cushing's syndrome patients. The low T3 syndrome was frequently seen (73.9%), whereas the incidences of leukocytosis and an increased level of basal plasma cortisol were relatively low (42.5% and 47.5%, respectively). Relative lymphopenia provides useful information for diagnosing Cushing's syndrome since it has high sensitivity although it should be kept in mind that its specificity is low.