Plasma arginine-vasopressin (AVP) was measured before and after 24 h of a 26-hour renal concentration test in 47 patients treated with lithium for 6–180 months (mean 70 months). In 34 of the patients, plasma AVP was also measured before and after a 2- to 4-hour period of water loading, and in 31 of the patients, creatinine, <sup>125</sup>iothalamate, <sup>131</sup>I-hippuran and lithium clearances were measured. Plasma AVP values were compared to those obtained in 8 healthy controls. Baseline AVP levels were significantly higher in the lithium-treated patients than in healthy controls. During the period of water deprivation AVP values increased significantly and during oral water loading a significant decrease took place, AVP values still being significantly higher in the lithium-treated patients than in the healthy controls. During oral water loading a slight increase in lithium clearance as well as fractional lithium excretion was seen as compared to values obtained during the last 2 h of a renal concentration test. This study demonstrates that antidiuretic hormone production is neither blocked nor inhibited during lithium treatment. The hypothalamic system reacts on water deprivation as well as on water loading. This study supports the notion that the main lithium-induced renal affection is a vasopressin-resistant impairment of renal concentrating ability.