OBJECTIVE: The aim of the present study was to test the hypothesis that glucocorticoid receptor mRNA concentrations decreased with increasing fatness in normal subjects. MEASUREMENTS: Serum leptin concentrations, fat distribution parameters, lymphocyte glucocorticoid (GCR) mRNA, b b 2 -adrenoceptor mRNA and c-fos mRNA concentrations measured by RT-PCR-HPLC. SUBJECTS: Fifteen healthy non-obese young subjects with a mean body mass index (BMI) of 23.5 AE 0.3 ( AE s.e.m.) kgam 2 . RESULTS: Lymphocyte GCR and b b 2 -adrenoceptor mRNA concentrations averaged 4.2 AE 0.2 ( AE s.e.m.) amolam mg total RNA and 1.4 AE 0.1 amolam mg total RNA, respectively. There was a signi®cant negative correlation between serum leptin and lymphocyte GCR mRNA (P`0.01). Serum leptin correlated positively with the waist ± hip ratio (P`0.03), whereas lymphocyte GCR mRNA correlated negatively to the waist ± hip ratio (P`0.04). Serum cortisol correlated with the weight of the subjects but not the waist ± hip ratio or GCR mRNA. CONCLUSIONS: It is suggested that the decrease in lymphocyte GCR mRNA concentration with increasing serum leptin concentrations is a counterregulatory response to an increased body fat content. Further studies are warranted, especially to elucidate the relationship between GCR mRNA in lymphocytes and in fat cells and to clarify the mechanism of the decrease in GCR mRNA.