Levels of total amino compounds (ninhydrinpositive substances, n.p.s.) have been measured in the inner medullas of rats during acute water diuresis and following the induction of hypovolaemic oliguria by the injection (i.p.) of 30% polyethylene glycol 20,000 (PEG) in 0.9% saline. Mean medullary fluid n.p.s. concentrations fell from 26.5 mmol to 15.2 mmol Gly equiv/l (-43%) within 2.5 h from the onset of diuresis, while the mean calculated tissue osmolality decreased from 738 mosmol/kg (control) to 369 mosmol/kg H2O. By 24 h n.p.s. and osmolality had returned to control levels. By 0.5 h after injection of PEG the mean concentration of n.p.s. had increased from 26.4 mmol to 32.7 mmol Gly equiv/l (+24%) and by 4 h had reached 60.4 mmol Gly equiv/l (+19%). During this time the calculated mean tissue fluid osmolality rose from 696 to 1037 mosmol/kg H2O. Levels of n.p.s. did not increase further for up to 12 h. It is proposed that losses of amino compounds may make a significant contribution to the overall decrease in medullary cellular osmotic potential accompanying reduced tissue fluid osmolality, and that increased levels of these solutes may provide short-term osmoprotection during antidiuresis of rapid onset, in contrast to the more slowly accumulating methylamines and polyhydric alcohols.