Human skeletal muscle expresses leptin receptor mRNA, however it remains unknown whether leptin receptors (OB-R) are also expressed at the protein level. Fourteen, healthy men (age = 33.1 ± 2.0 yr, height = 175.9 ± 1.7 cm, body mass = 81.2 ± 3.8 kg, body fat = 22.5 ± 1.9%; mean ± s.e.m.) participated in this investigation. The expression of OB-R protein was determined in skeletal muscle, subcutaneous adipose tissue and hypothalamus using a polyclonal rabbit anti-human leptin receptor. Three bands with a molecular weight close to 170, 128 and 98 KDa were identified by Western blot with the anti-OB-R antibody. All three bands were identified in skeletal muscle, the 98KDa and 170KDa bands were detected in hypothalamus and the 98KDa and 128 KDa bands were detected in thigh subcutaneous adipose tissue. The 128 KDa isoform was not detected in four subjects, while in the rest its occurrence was fully explained by the presence of intermuscular adipose tissue as demonstrated using an antiperilipin A antibody. No relationship was observed between the basal concentration of leptin in serum and the 170 KDa band density. In conclusion, a long isoform of the leptin receptor with a molecular weight close to 170 KDa is expressed at the protein level in human skeletal muscle. The amount of 170 KDa protein appears to be independent of the basal concentration of leptin in serum.