The callipyge mutation in sheep is a polar overdominant mutation that results in post-natal muscle hypertrophy in the loin and hindquarters of paternal heterozygotes (+/CLPG). Sheep that are homozygous for the callipyge allele (CLPG/CLPG) do not express the muscle hypertrophy phenotype, but serve as carriers for the mutation. Callipyge sheep are characterized by improved feed efficiencies and leaner carcasses. Leptin is a protein hormone secreted from adipose tissue and has been found to affect appetite and serve as an indicator of body fat mass. To date, very little knowledge is available as to the effect of the callipyge mutation on circulating leptin levels. Due to the interaction of leptin with feed intake and energy availability, and the fact that the majority of fetal growth occurs in late gestation, it is important to understand if the callipyge mutation interacts with leptin production in late gestational ewes. Therefore, our objective was to characterize serum concentrations of leptin in late gestational callipyge ewes vs. non-callipyge ewes. We evaluated genetically verified callipyge (n = 6), homozygous (n = 8) and normal (n = 8) ewes weekly during the last eight wks of gestation through one wk post-partum. Weights were taken and body condition scores were assigned by trained personnel weekly. Blood was collected via jugular venipuncture on each sampling date and subjected to an ovine-specific leptin RIA. Genotype influences on peripheral concentrations of leptin were found to be highly significant (p = 0.0005). Total leptin means for +/CLPG were 5.41±0.40 ng/ml, CLPG/CLPG 8.11±0.70 ng/ml, and +/+ 9.13±0.93 ng/ml. Sampling date was also significant (p = 0.0098) with all ewes showing a decrease in leptin levels throughout gestation and parturition. Using repeated measures, we were able to detect lower levels of plasma leptin in callipyge ewes, which may be indicative of their lower overall body fat content. These results indicate that the callipyge phenotype decreases the levels of adipose tissue and leptin production in gestating ewes.