Depressed heart rate variability (HRV) has been associated with adverse outcome during and after acute myocardial infarction (AMI). The effects of reperfusion in AMI on the course of HRV have not been well characterized as yet. We analyzed 123 consecutive patients with a first AMI who underwent successful reperfusion (Thrombolysis In Myocardial Infarction grades 2 and 3) by primary percutaneous transluminal coronary angioplasty (PTCA). Time- and frequency-domain HRV was measured from 24-hour Holter monitoring, which began at hospital admission. Mean RR interval increased significantly after successful PTCA. Reperfusion immediately caused an immediate transient depression of HRV, which was followed by a significant increase of HRV. Quantitative markers of sympathetic activity and sympathovagal balance, such as SD of the averages of NN intervals in all 5-minute segments, and low- and/or high-frequency ratio continuously decreased within the observation period. Patients with anterior AMI exhibited the same pattern of temporal changes of HRV, with, however, lower absolute values for HRV and mean RR interval than patients with non-anterior AMI. Subgroup analysis in 21 patients with reperfusion > 12 hours after onset of pain showed that the biphasic profile of HRV and the marked increase of mean RR interval was absent. Furthermore, in patients with late reperfusion, HRV was significantly lower compared with those with early reperfusion. Thus, timely reperfusion in AMI leads to a biphasic effect on autonomic tone, characterized by a transient suppression, followed by a significant activation of the vagal tone, as well as an attenuation of sympathetic activity. Recovery of HRV may contribute to the benefits of early reperfusion in AMI.