The rat has been a useful model for studying neuronal and metabolic abnormalities associated with fetal and neonatal hypothyroidism produced by treatment of the mother with antithyroid medication. The neonates are then maintained on this medication via the mother's milk until weaning and subsequently through the drinking water. We have determined the concentrations and contents of immunoreactive cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in the brain and gut of groups of rats exposed to antithyroid medication from day 16 of gestation. The neonates were sacrificed at 2, 4, 8 and 12 weeks. Compared to controls total body weight was greatly reduced in methimazole (MMI)-treated rats, all of whom were hypothyroid as evidence by marked reduction of T4 and increase in TSH. Discontinuation of MMI-treatment after 8 weeks resulted in normalization of T4 and TSH and a dramatic weight gain but at 12 weeks the brain weights of the MMI-treated rats were reduced by 17% and the brain contents, of CCK and VIP were similarly reduced. Tissue weights throughout the gut were 1/2 or less than those of control rats. Since VIP but not CCK concentrations in the gut of MMI-treated animals were significantly greater than those of the control animals, it would appear that there was greater loss of mucosal tissue with its endocrine content of CCK than of neuronal tissue with its greater content of VIP. Because of marked differences in body weight this model does not permit distinction between a direct effect of MMI-treatment per se or the effect of reduced food intake on the diminution of CCK and VIP content of the brain and gut.