The purpose of this study was to investigate the use of [1-11C]acetate as a metabolic tracer for renal imaging in human subjects. METHODS Eighteen patients underwent dynamic PET imaging of the kidneys after intravenous bolus injection of 10-20 mCi [1-11C]acetate. Time-activity curves of renal parenchyma tracer activity were fitted to a two-compartment model using direct arterial blood sampling for the arterial input function. RESULTS Renal uptake of [1-11C]acetate is prompt and high target-to-background ratios are achieved even in the presence of markedly reduced renal function. Carbon-11-acetate is cleared from the renal parenchyma without any urinary excretion and the rate of clearance is comparable to myocardial clearance rates. Among normal subjects, K1, ranged from 0.653 to 1.37 ml/min-g, and was reduced to as low as 0.363 ml/min-g in severe renal disease (serum creatinine greater than 5 mg/dl), while k2 ranged from 0.114 to 0.166 min-1 among normal subjects and was reduced to as low as 0.053 min-1 in severe renal disease. Kinetic parameters K1 and k2 were both reduced in the presence of intrinsic renal disease or significant renal artery stenosis. Renal cell carcinoma demonstrated similar uptake of [1-11C]acetate, but substantially reduced the rate of clearance compared to normal and diseased non-neoplastic renal tissue, allowing for ready differentiation of renal cell carcinoma from non-neoplastic renal tissue on images acquired beyond 10 min of tracer administration. CONCLUSIONS Carbon-11-acetate is a promising physiologic tracer for the study of renal disease.