In humans, sex steroid-binding protein (SBP) is a protein from the liver which binds with high affinity sex steroid hormones. The plasma concentration of SBP is regulated in part by hormonal factors. It has been shown that estrogens and/or thyroid hormones increase the production of SBP by hepatoma cell lines. It is therefore assumed that the increase in SBP levels in patients given oral estrogens or thyroid hormones is the consequence of a direct stimulation of the liver production of SBP by these hormones. The effects of androgen, progestagen and glucocorticoid hormones are unclear or still a matter of controversy. Moreover, the regulation of the metabolic clearance rate of SBP and the influence of nonhormonal factors on the production of SBP are still speculative. Changes in SBP have been described in a few nonendocrine diseases. A slight hormonal dysfunction may be either the primary or the sole cause of the changes in SBP occurring in these diseases. As an example, elevated SBP levels have been reported in men with liver cirrhosis together with testicular hypofunction and increased estrogen levels. It is therefore difficult to demonstrate that the increase in SBP is due to the liver dysfunction rather than to the endocrinological side effects of cirrhosis. The aim of this review is to present some aspects of the nonhormonal regulation of SBP. There is accumulating evidence in the literature for a relation between SBP levels and body weight and fat distribution, energy balance, diet and physical activity, and lipid metabolism. Therefore, it is tempting to propose that SBP is an index which reflects the status of endocrine, metabolic and nutritional functions. Measurement of SBP may be considered of interest in the light of previous epidemiological studies and the preventive approach to diseases such as hormone dependent tumors, cardiovascular diseases and osteoporosis.