To examine the relationship between PRL and the mitogenic capacity of lymphocytes, we studied the relationships among circulating PRL levels, somatic growth, and the response of splenic lymphocytes to the mitogen phytohemagglutinin (PHA) in hamsters. In the first experiment, no differences were observed in the PHA responses of lymphocytes removed from intact or hypophysectomized-orchidectomized hamsters. No relationships were observed between circulating PRL levels and either the PHA responses or somatic growth. However, significant positive correlations were observed between the somatic growth of intact or hypophysectomized-orchidectomized hamsters and the PHA responses (r = 0.741; P less than 0.01 for intact hamsters; r = 0.642; P less than 0.01 for hypophysectomized-orchidectomized hamsters). In three subsequent experiments we tested the effects of placing muscle or hypophysial allografts in hypophysectomized-orchidectomized hamsters on somatic growth, the PHA responses, and circulating PRL levels. Neither type of allograft altered the somatic growth of hypophysectomized-orchidectomized hamsters. The hypophysial allografts did elevate serum PRL levels. In all experiments the responses of splenic lymphocytes to PHA showed a significant positive correlation with somatic growth, but not with serum PRL levels. These results minimize a role of PRL in this particular lymphocyte response. The results suggest that a strong correlation exists between mechanisms responsible for somatic growth in hypophysectomized-orchidectomized hamsters and the immune status, as determined by the response to PHA, of the animals. This relationship also may exist in intact hamsters.