Human growth hormone (GH) is a 22kD monomeric protein produced and stored in somatotrophs in the anterior pituitary gland. GH is released from the pituitary into the bloodstream in a pulsatile manner under the regulatory control of hypothalamic somatostatin (SS) and GH-releasing factor (GHRF). The timing and frequency of GH release appears to be regulated by somatostatin, while the amplitude of GH release is determined by GHRF. A minor fraction (~10%) of GH in circulation exists in a smaller 20kD form. GH has profound effects on tissue growth and metabolism, which is thought to be mediated through GH-dependent production of IGF-I and IGF-II, and their associated binding proteins. GH apparently stimulates IGF production after binding to specific cell surface receptors in the liver and, possibly, other tissues. Almost 50% of GH in circulation is bound to a high affinity GH binding protein (GHBP), which represents the extracellular domain of the GH receptor. Deficient GH secretion can occur in a number of clinical conditions. However, evaluation of GH deficiency is complicated by the episodic nature of GH secretion and low circulating levels. A variety of physiologic and pharmacologic stimuli have been used to stimulate pituitary GH release during testing and failure to achieve a normal serum GH level in response to at least 2 GH stimulation or provocative tests is considered to be a diagnostic of GH deficiency. The definition of a normal serum GH response is controversial, although published values generally range from 5-10ng/ml. GH excess (or acromegaly) can be caused either by direct GH hypersecretion or GH excess secondary to GHRF hypersecretion.