The reliability of the use of p-aminohippurate (PAH) as a clearance marker for the determination of renal plasma flow during saline or dextrose infusion was investigated in conscious and anaesthetized rats. In the conscious rat (wt. 350-400 g) infused for 4 h with 0.85% saline followed by 3 h of 2.5% dextrose, PAH clearance averaged 11.50 +/- 1.45 ml/min during saline infusion and 7.83 +/- 0.82 ml/min during dextrose infusion. The difference was significant (P less than 0.02). Inulin clearance, however, was unchanged. With dextrose as the initial infusate, PAH clearance averaged 5.86 +/- 0.65 ml/min and increased (P less than 0.01) to 8.74 +/- 0.71 ml/min following a change of infusate to saline, although inulin clearance was again unchanged. In separate groups of rats anaesthetized with sodium pentobarbitone, a comparison was made between renal blood flow values calculated from PAH clearance and haematocrit, and those determined simultaneously using an electromagnetic flow probe placed on the left renal artery. During 0.85% saline infusion, the calculated value was 88.1 +/- 8.4% of that measured using the flow probe. During 2.5% dextrose infusion the value determined from PAH clearance was only 47.3 +/- 4.2% of that obtained using the flow probe, and this is significantly (P less than 0.01) lower than the ratio found during saline infusion. In another study, renal venous blood samples were obtained from sodium-pentobarbitone-anaesthetized rats during 0.85% saline or 2.5% dextrose infusions, for calculation of the renal PAH extraction ratio. During saline infusion, PAH extraction averaged 68.3 +/- 2.5%, whereas during dextrose infusion PAH extraction was lower (P less than 0.001) and averaged only 48.8 +/- 3.2%. It is concluded that PAH clearance grossly underestimates renal plasma flow during 2.5% dextrose infusion in the rat.