We estimated the changes of fluid compartment volumes and concomitant effects on plasma atrial natriuretic peptide (ANP) and plasma renin activity (PRA) for up to 4 hr after intravenous infusion of 57 ml/kg of 1.5% glycine solution over 40 min in six conscious ewes. Infusions of the same volumes of isotonic saline served as controls. Glycine infusions resulted in a four-fold increase and saline in a doubling of the plasma ANP concentration, despite a more pronounced volume expansion from saline. The ANP level remained significantly elevated for 2 hr after glycine infusion. This result suggests that glycine has a specific ANP-stimulating effect which may contribute to the hypovolemia, hypotension, and natriuresis seen in the "transurethral resection (TUR) syndrome." The PRA decreased by about 50% in response to both infusions. However, PRA returned to the baseline level at the end of the glycine infusion, whereas it remained depressed during the entire follow-up period after saline infusion. This is in accordance with a pure volumetric influence on renin release, since calculations of fluid distribution between different compartments suggested that, in contrast to the effect of saline, only a small amount of irrigant water remained in the extracellular fluid after glycine administration. The urea and creatinine clearances increased only in response to isotonic saline. Glycine infusion was even followed by reduction of the creatinine clearance.