To clarify the clinical significance of Tl-201 reverse redistribution (RR), 33 patients with chronic coronary artery disease (CAD) underwent stress-redistribution Tl-201 cardiac imaging with rest reinjection, coronary arteriography, and 2D-echocardiography. Rest Tc-99m MIBI scintigraphy was also performed in 27 of the 33 patients. A total of 495 segments were analyzed for Tl-201 scintigraphy (405 for Tc-99m MIBI). Each segment was assigned to one of the major coronary artery territories. Two patterns of RR were identified; 1) pattern A (RR-A) showed normal Tl-201 uptake on stress images and lower than normal on redistribution images, and 2) pattern B (RR-B) showed lower than normal Tl-201 uptake on stress images with further decrease on redistribution images. The RR phenomenon was found in 46 (9% of the total) segments; 25 with RR-A and 21 with RR-B. Reverse redistribution pattern A segments had lower Tc-99m MIBI uptake (84 +/- 9% versus 92 +/- 10%, P < 0.0001) and a higher percentage of stenosed coronary arteries (80% versus 49%, P < 0.05) compared to normal segments (n = 204, 41% of the total). No difference in wall motion was observed between RR-A and normal segments. Of the 25 segments with RR-A, 14 showed enhanced Tl-201 uptake after reinjection (Re+) and 11 remained unchanged after reinjection (Re-). Segments that were Re- showed significantly (P < 0.05) lower Tc-99m MIBI uptake (79 +/- 9%) compared to Re+ segments (87 +/- 8%) and normal segments (92 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS)