The effect of perinatal hypothyroidism on the number and distribution of hippocampal kainic acid binding sites was examined in rats. Timed pregnant Sprague-Dawley rat dams were given water containing either 0.02% propylthiouracil (PTU) or untreated water from gestational day 18 until their litters were weaned at postnatal day 31. The offspring were sacrificed at 31 or 120 days of age, blood samples collected and their brains frozen. In the 31-day-old rats, serum thyroxine, serum triiodothyronine, total body weight and whole brain weight all indicated that the PTU-treated rats were hypothyroid. Hippocampal kainic acid binding was analyzed in sections of dorsal and ventral hippocampal formation by in vitro 3H-vinylidene kainic acid (VKA) autoradiography. Compared to the untreated controls, specific 3H-VKA binding was reduced by 43% in the ventral hippocampal formation stratum lucidum of 31-day-old FΓU-treated rats. Specific 3H-VKA binding was not different in the dorsal hippocampal formation. Saturation of 3H-VKA binding studies indicated that the decrease – induced by PTU treatment – in ventral hippocampal 3H-VKA binding was due to a reduction in the total number of 3H-VKA binding sites. At 120 days of age, 3 months after the cessation of the PTU treatment, serum thyroid hormone levels were not different than those of controls, indicating a recovery of thyroid hormone function after the perinatal PTU treatment. However, specific 3H-VKA binding remained significantly reduced in the ventral hippocampal formation of 120-day-old rats. This observation indicated that the decrease in 3H-VKA binding at 31 days of age was not simply due to a delay in the development of this system and that perinatal hypothyroidism can cause long-lasting alterations in the total number of hippocampal kainic acid binding s