Significant uptake and retention of 99Tc(m)-dextran (molecular weight: 81,000) in renal parenchyma was discovered during evaluation of its intravascular use. Renal SPET images confirmed this. This study was designed to evaluate 99Tc(m)-dextran as a renal cortex imaging agent. Stability of parenchymal retention was shown by insignificant outflow at 24 h and by frusemide intervention. Evaluation of the renal parameters of intravenous 99Tc(m)-dextran (n = 71 normal kidneys) and its comparison with 99Tc(m)-DTPA n = 10) and 99Tc(m)-DMSA(III) (n = 23) was undertaken. The early glomerular extraction phase of the renograms of 99Tc(m)-DTPA and 99Tc(m)-dextran appeared identical; parenchymal uptake of 99Tc(m)-dextran continued to increase and reached a near-plateau by 40-60 min. The mean cortex-to-background and cortex-to-liver ratios at 2 h with 99Tc(m)-dextran and 99Tc(m)-DMSA(III) were 14.9 and 9.2, and 16.0 and 8.9, respectively. The target-to-nontarget ratios were similar despite different absolute renal uptake values (12 vs 20% at 2 h) because of faster background clearance of 99Tc(m)-dextran. The mechanism of parenchymal retention of 99Tc(m)-dextran appears to be trapping at the endothelial-epithelial interphase of the glomerulus. Our initial experience suggests 99Tc(m)-dextran is a viable renal parenchyma imaging agent.