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Male Wistar rats were fed a lithium diet for 2–3 months producing marked polyuria (> 75 ml/100 g in 24 h) and a plasma Li concentration of 0·7 mmol/l. In acute experiments animals were anaesthetized with 5-ethyl-5-(1-methylpropyl)-2-thiobarbituric acid and infused with hypotonic glucose–saline (15 ml/h). Addition of prostaglandin A₂ (PGA₂; 0·2 ng/min) for 180 min to the infusate did not restore the impaired antidiuretic response to arginine-vasopressin (AVP) whether this agent was infused continuously (150 µu./min) or given as bolus injections (2500 µu.). In long-term experiments animals were kept in metabolism cages and Alzet osmotic minipumps were implanted for intravenous infusion of drugs at 1 µl/h. Again, PGA₂ infusion at 0·2 ng/min failed to restore the impaired antidiuretic response to AVP (150 µu./min). It was therefore concluded that in rats with severe polyuria induced by long-term administration of lithium, infusion of PGA₂ at 0·2 ng/min cannot restore the impaired response to antidiuretic hormone as has been reported by others.