Glucocorticoids play an important role in determining body composition. A polymorphism of the glucocorticoid receptor gene (in codons 22 and 23) has previously been found to be associated with relative glucocorticoid resistance, low cholesterol levels, and increased insulin sensitivity. In this study, we investigated whether this ER22/23EK polymorphism is associated with differences in body composition and muscle strength. We studied a cohort of 350 subjects who were followed from age 13 until 36 yr. We compared noncarriers and carriers of the ER22/23EK variant in anthropometric parameters, body composition, and muscle strength, as measured by arm pull tests and high jump from standing. We identified 27 (8.0%) heterozygous ER22/23EK carriers. In males at 36 yr of age, we found that ER22/23EK carriers were taller, had more lean body mass, greater thigh circumference, and more muscle strength in arms and legs. We observed no differences in body mass index or fat mass. In females, waist and hip circumferences tended to be smaller in ER22/23EK carriers at the age of 36 yr, but no differences in body mass index were found. Thus, the ER22/23EK polymorphism is associated with a sex-specific, beneficial body composition at young-adult age, as well as greater muscle strength in males.