Simultaneous [14C]inulin and exogenous creatinine clearance procedures were performed on 10 healthy adult dogs of both sexes after constant IV infusions of inulin and a single subcutaneous injection of creatinine. For 30 clearance procedures determined for 10 dogs, the creatinine/inulin (C/I) clearance ratio was 1.03 +/- 0.01, and the results of the 2 tests were highly correlated (r = 0.91). Simultaneous [14C]inulin and endogenous creatinine clearance procedures were performed in the same 10 dogs. For 30 clearance procedures in these dogs, the C/I clearance ratio was 0.70 +/- 0.06 and the 2 tests were less highly correlated (r = 0.79). Fifteen clearance procedures of the same design were conducted on 5 dogs with azotemia induced by surgical reduction of renal mass. In these dogs, the exogenous C/I clearance ratio was 1.09 +/- 0.12, and the endogenous C/I clearance ratio was 0.89 +/- 0.07. It was concluded that the single injection method of exogenous creatinine clearance was a valid method for clinical measurement of glomerular filtration rate in the female dog and would closely approximate glomerular filtration rate in male dogs without azotemia. At normal or near normal plasma creatinine levels, the endogenous creatinine clearance procedure gave erroneously low values for glomerular filtration rate when the common methods of creatinine analysis were used.