Chronic cold exposure causes hypertension and diuresis. The aim of this study was to determine if vasopressin plays a role in cold-induced hypertension (CIH) and diuresis. Two groups of Long-Evans (LE) and 2 groups of homozygous vasopressin-deficient Brattleboro (VD) rats were used. Blood pressure (BP) was not different among the 4 groups during a 2-week control period at room temperature (RT, 25°C). Following the control period, 1 LE and 1 VD groups were exposed to cold (5°C) while the remaining groups were kept at RT. BP and body weight were measured weekly during exposure to cold. Food intake, water intake, urine output and urine osmolality were measured during weeks 1, 3, and 5 of exposure to cold. At the end of week 5, all animals were killed and blood was collected for measurement of plasma arginine vasopressin (AVP). Kidneys were removed for measuring renal medulla V₂ receptor mRNA and aquporin-2 (AQP-2) protein expression. It was found that BP of both LE and VD rats increased significantly within 2 weeks of exposure to cold and reached a high level by 5 weeks. Both LE and VD rats developed elevations of BP at approximately the same rate and to the same degree. Vasopressin deficiency significantly increased urine output and solute-free water clearance and decreased urine osmolality. Chronic cold exposure increased urine output and solute-free water clearance and decreased urine osmolality in LE rats, indicating that cold exposure caused diuresis in LE rats. In contrast, cold exposure failed to affect the above parameters in VD rats, suggesting that the AVP system is responsible for cold-induced diuresis. Cold exposure did not alter plasma AVP level in LE rats. However, renal medulla V₂ receptor mRNA expression level and AQP-2 protein expression level were decreased significantly in the cold-exposed LE rats, suggesting that cold exposure inhibited renal V₂ receptors and AVP-inducible AQP-2 water channel. Conclusions: (1) AVP may not be involved in the pathogenesis of CIH; (2) The AVP system plays a critical role in cold-induced diuresis; (3) Cold-induced diuresis is due to suppression of renal V₂ receptors and associated AQP-2 water channel rather than inhibition of AVP release.