While the effect of sex steroids on growth is well known, their effects on somatomedin C, a mediator of growth, are unclear. To investigate the effect of sex steroids on somatomedin C (Sm-C) concentrations, Sm-C was measured in adults receiving pharmacological doses of various sex steroids (estrogens, testosterone, and medroxyprogesterone acetate). Testosterone therapy had no effect on the somatomedin C concentration. Although both estrogen and medroxyprogesterone acetate therapy reduced the plasma testosterone concentration into the normal female range, they had different effects on Sm-C concentrations. Estrogen therapy produced no detectable change in the Sm-C concentration; medroxyprogesterone acetate caused an increase in the plasma somatomedin C concentration (P less than 0.001). Since medroxyprogesterone acetate also does not increase the serum GH concentration, other mechanisms by which medroxyprogesterone acetate stimulates Sm-C production are discussed.