The gastrointestinal peptides secretin and cholecystokinin were found to inhibit the incorporation of 3H-thymidine in the lymphocyte transformation reaction in response to phytohemagglutinin. Both peptides inhibited lymphocyte activation in a dose responsive fashion. This inhibition was not due to the toxicity of these substances, as the lymphocytes remained intact and capable of excluding trypan blue. Neither glucagon nor gastrin had any effects of lymphocyte transformation.