Determination of creatinine clearance (Ccr) is not a reliable indicator of glomerular filtration rate (GFR), owing to tubular secretion of creatinine. It has been reported that Ccr measurements can approximate true GFR after cimetidine (Ci) administration., In this study, GFR was estimated by Cockcroft and Gault's equation (CC-G) based on measurement of plasma creatinine, and Ccr was determined by the standard clearance equation using 4- and 24-hr urine samples (Ccr(4) and Ccr(24), respectively) in 17 patients and 10 healthy controls. After cimetidine administration (800 mg, 3 times daily), GFR values were recalculated at the same time periods (CCiC-G, Ccr(Ci4) and Ccr(Ci24), respectively). The results were all compared to those obtained by the Tc-99m-DTPA protein-free double-sample method (C-DTPA), which is a reference method for GFR determination. The coefficient of variation (CV%) for Ccr(24)/C-DTPA was high before cimetidine administration; C-cr24 and Ccr(Ci24) values were significantly different from C-DTPA (CV 23.1%, Ccr(24)/C-DTPA = 1.17, p 0.005; and CV 14.1%, Ccr(Ci24)/C-DTPA = 0.92, p 0.006, respectively). Ccr(4) values obtained before cimetidine ingestion showed large variation and were significantly different from C-DTPA (CV 15.5%, Ccr(4)/C-DTPA = 1.11, p 0.001). Ccr(Ci4) values after cimetidine were similar to C-DTPA (CV 6.9%, Ccr(Ci4)/C-DTPA = 1.01, p 0.28). CC-G estimates were higher before cimetidine intake (CV 12.4%, CC-G/C-DTPA = 1.21; p <0.001), whereas CCiC-G values were not significantly different from C-DTPA values (CV 7.0%, CCiC-G/C-DTPA = 1.01, p 0.67). This study shows that GFR estimations by CC-G, Ccr(4), Ccr(24), or Ccr(Ci24) are insufficiently reliable. On the other hand, CCiC-G and Ccr(Ci4) results are acceptable for true GFR estimations.