To determine putative effects of various protocols of propylthiouracil (PTU)-induced hypothyroidism on vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) levels in the atria of developing and adult female rats.Perinatal hypothyroidism was induced by treating pregnant rats with 0.05% PTU in drinking water from late gestation till the age of 60 days (P-PTU). Adult rats were given PTU for 10, 30 or 70 days (PTU-10, PTU-30 and PTU-70, respectively). Corresponding age-matched controls were left intact (P-Cont, Cont-10, Cont-30 and Cont-70, respectively). Resting heart rate, serum total thyroxine concentration, body weight and atrial weight were determined in all animals. VIP-LI levels in tissue extracts were measured by radioimmunoassay.The values of heart rate, serum total thyroxine, body weight and atrial weight showed that 10-day treatment did not suppress thyroid gland function completely. However, the remaining experimental protocols were sufficient to reach stable hypothyroid conditions. Thyroid hormone deficiency led to a significant increase in VIP-LI levels in both atria of PTU-30 and PTU-70 rats (P<0.01 versus corresponding controls). Interestingly, in P-PTU atria, VIP-LI reached significantly higher values than in rats treated with PTU for the same time during adulthood (PTU-70).These results provide new evidence that hypothyroidism interferes with VIP-ergic innervation in rat heart atria. The impact of thyroid hormone deficiency on VIP-LI levels differed in P-PTU and PTU-70 rats suggesting that thyroid hormone may play an important part in the development of VIP-ergic innervation in rat heart atria.