Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Cushing's syndrome is a disease state usually associated with weight gain due to the accumulation of adipose tissue. In order to study the effect of chronic glucocorticoid excess upon serum leptin levels; in the present work, four patients with recently diagnosed Cushing's syndrome and a group of control subjects matched for age, sex and body mass index (BMI) were studied. Serum leptin concentrations, measured by radioimmunoassay, were assessed in samples taken every 60 minutes over a 24 hour period. Assessment of leptin concentrations over 24 hours, by means of the area under curve showed a twofold increase in serum leptin levels in patients with Cushing's syndrome (mean+/-SEM 54.3+/-14) in comparison to control subjects (29.3+/-4.4; p<0.05). In conclusion, our data show that leptin levels are markedly increased in Cushing's syndrome patients. The relevance of this finding to the increased body fat present in patients with Cushing's syndrome merits further studies.