Because animal experiments have suggested that PRL might regulate the serum somatomedin (SM) concentration, the effect of sustained hyperprolactinemia on the serum SM level was studied in patients with proven pituitary microadenomas. PRL was determined by RIA. SM was measured on the same sample by a human placental membrane radioreceptor assay in which all SMs cross-react. The mean serum SM (+/-SE) in 16 females with elevated PRL levels from 68--21,000 ng/ml was 0.97 +/- 0.08 U/ml. This was not statistically different from that of 29 normal women, (P greater than 0.2). The mean SM for the 3 male patients with serum PRL levels from 570--5,050 ng/ml was in the lower range for normal males. There was no correlation in either group between the serum SM and PRL levels. These results indicate that PRL is not a major regulator of the serum SM concentration in man.