Serum concentrations of immunoreactive somatomedin C were determined in 78 patients with pituitary tumors or craniopharyngiomas. Patients with large tumors, GH deficiency, and normal PRL levels (group 1) had low somatomedin C concentrations (mean, 0.23 U/ml; n = 23). Group 2 included patients with large PRL-secreting pituitary tumors and GH deficiency. This group had serum somatomedin C concentrations in the normal adult range (mean, 1.01 U/ml; n = 20). Patients with hyperprolactinemia and normal pituitary GH secretion (group 3) also had somatomedin C concentrations which were normal (mean, 1.47 U/ml; n = 17). As a group, these values were slightly greater than those of the GH-deficient patients with hyperprolactinemia (P less than 0.05), but not significantly different from a fourth group of patients with tumors, normal pituitary function, and normal PRL levels (mean somatomedin C, 1.40 U/ml; n = 18). It is concluded that significantly increased concentrations of human PRL have the capacity to raise serum somatomedin C concentrations into the normal range in individuals with GH deficiency. In patients with normal pituitary function, however, this weak stimulator of somatomedin C has no detectable effect.