The effects of estrogen, androgen, cortisol, growth hormone and thyroid on the connective tissue of the skin have been studied by means of serial skin biopsy in patients with spontaneous hypo- or hyperfunctioning syndromes prior to and following definitive therapy with specific replacement therapy or following treatment for glandular hyperactivity. Estrogen and androgen induce edema and subsequent thickening of the collagen bundles in the skin of patients with hypogonadism. In the subject with hyperthyroidism, minimal metachromasia is observed in the cutis in contrast with the abundant amounts seen in hypothyrodism, and the collagen bundles are rather thin. Following cure of the thyrotoxicosis, the collagen bundles become much thicker. Marked thinning of the collagen is noted in the presence of excessive quantities of cortisol (Cushing's syndrome), and a reversion to a more normal picture is noted following cure. Acromegaly is characterized by the presence of densely packed collagen bundles in the skin.