Aging is associated with a progressive decline in GH secretion and serum insulin-like growth factor (IGF)-I levels. This change in the GH-IGF axis is thought to contribute to the changes in body composition associated with aging, such as a loss in lean body mass and an increase in adipose tissue mass. Although the decrease in GH secretion starts in the third decade of life, marked changes in muscle mass and strength become apparent only much later. To assess whether a component of GH resistance supervenes in senescence, we studied plasma GH binding protein (GHBP) levels in 50 normal subjects between the ages of 61 and 98 yr. The GHBP is a soluble, circulating ectodomain of the GH receptor (GHR); its plasma level is thought to reflect GHR levels in tissues and, hence, GH responsivity. GHBP activity in plasma declined progressively between age 60 and 98 yr. The GHBP levels in nonagenarians was about half that of persons aged 60-65. This contrasts with younger adults, where GHBP levels remain relatively stable between the ages of 20 and 60. We conclude that in advanced age. GHBP and, by inference, GHR levels, decrease, which may add an element of GH resistance to the already compromised GH secretion status, thereby further contributing to the changes in body composition and frailty in the elderly.