The Maze III procedure is a surgical operation for curative treatment of AF. The procedure is extensive, however, with multiple incisions in both atria, and its effects on autonomic regulation of the heart rhythm are not known. This study comprises 17 patients, 10 with paroxysmal AF and 7 with chronic AF, who had no concurrent cardiac disease known to affect heart rate variability (HRV). A 24-hour Holter recording was performed preoperatively and 2 months (early) and 7 months (late) after surgery, for analysis of HRV in the time and frequency domains. Early after the Maze procedure all HRV components were markedly reduced compared to baseline (mean +/- 1 SD): SDNN 73 +/- 13 versus 148 +/- 50 (ms), total power 168 +/- 126 versus 560 +/- 1567 (ms2), low frequency (LF) power 47 +/- 67 versus 826 +/- 677 (ms2), high frequency (HF) power 47 +/- 40 versus 678 +/- 666 (ms2), and LF:HF 1.22 +/- 0.9 versus 2.55 +/- 1.4. Late after the Maze procedure all variables were still reduced. Only total power increased significantly between early and late follow-up (168 +/- 126 vs 496 +/- 435 ms2). Late after Maze surgery, values of the different HRV components did not differ between the patients with paroxysmal AF and chronic AF. Early after the Maze procedure there is a marked decrease of all HRV components, which is maintained 7 months after surgery, a pattern consistent with denervation of the heart.