The renal clearance of inulin (ClIN) was measured in anaesthetized male rats using a continuous intravenous infusion method.ClIN was independent of urine flow rate provided this was greater than 003 ml/ minute.At flow rates lower than this, CIIN was reduced and appeared to correlate with the rate of flow.In experiments where a constant kidney function is required. e.g., pharmacokinetic studies, it is advisable to maintain urine, flow rates in the rat above-0-03 ml/minute.We are currently studying the distribution kinetics of neostigmine bromide in the rat. The clearance of inulin (CIIN) is monitored routinely in this work to assess renal function. For inulin, the clearance should be independent of plasma concentration and urine flow rate; Harvey & Malvin (1965) reported that in rats there is a lack of correlation between inulin clearance and flow rate. However, in the present distribution studies it was noted that at low rates of urine flow CIN was reduced and correlated with flow. These, results are reported here.Methods.-The method for the measurement of clearance was essentially that of Harvey & Malvin (1965). Male Wistar rats weighing 320-420 g were anesthetized by an intraperitoneal injection of ethyl carbamate (1-4 g/kg).The trachea, jugular vein, carotid artery and both ureters were cannulated with polyethylene tubing (Portex, PP50 In some experiments after measuring three control clearance periods neostigmine bromide C-14 was administered intravenously (10 jug/ 100 g or 20 ug/ 100 g body weight). In these experiments and also those of control groups the infusion rate was either 0-038 or 0075 ml/minute. In other experiments urine flow rate was altered by changing the infusion rate randomly in the range 0 009-0 075 ml/ minute. In these experiments arterial blood pressure (1 mmHg-=1333 mbar) was monitored from the carotid artery by means of a Condon manometer, arterial blood samples being obtained for assay from the femoral artery.The radioactive inulin was measured in plasma and urine samples using a Nuclear Chicago Unilux II liquid rcintillation spectrometer. Samples (0(05 ml) were assayed in a Triton X-100 scintillant (666-6 ml toluene, 333*3 ml Triton X-100 and 6 g butyl P.B.D. [2(4'-t-butyl phenyl)-5(4" biphenylyl)-1,3,4, oxadiazole]. All samples were corrected for quenching by the external standard ratios method.Results.-In control experiments, CIIN was measured at a constant infusion rate, mean urine flow was about 003 ml/min, CIIN was fairly constant and apparently independent of urine flow.In the first experiments in which neostigmine was administered the infusion rate of inulin was 0038 ml/minute. The CIIN fluctuated about the mean for any particular experiment, notably after the rapid intravenous ixljection of neostigmine. After neostigmine, the mean urine flow rate was only about 0015-0020 ml/min and the CGIN appeared to correlate with the flow rate. In later experiments infusion rate was raised to 0 075 ml/min to produce flow rates comparable to the controls. The C1IN was then fairly constant, ...