BACKGROUND: Reduced heart rate variability after acute myocardial infarction is an important risk stratification factor for mortality and life threatening ventricular arrhythmias. In recent years, thrombolytic therapy has revolutionized the therapy of acute myocardial infarction. However, there is little information about the mechanism of the beneficial effect of thrombolysis on cardiovascular mortality. This study was launched to investigate the relationship between thrombolytic therapy and cardiac autonomic activity, and the sequential changes in heart rate variability after acute myocardial infarction. METHODS: From October 1994 to July 1995, all consecutive patients with their first acute myocardial infarction were prospectively enrolled into the study. Patients without contraindication underwent thrombolytic therapy within six hours of the onset of symptoms. Other patients received conventional treatment. Ambulatory electrocardiography (EKG) was recorded on each patient 7, 90 and 180 days after acute myocardial infarction. Heart rate variability in time- and frequency-domain was analyzed. RESULTS: A total of 49 patients, 45 males and 4 females, were included in this study. The short-term heart rate variability (HRV) (seven-day) in the thrombolytic group was significantly higher than in the nonthrombolytic group in SDANN and SDNN. No significant difference in rMSSD, pNN50, LF, HF or LF/HF ratio was found. The location of MI did not influence the short-term HRV following acute myocardial infarction. In patients treated with thrombolytic agent, the follow-up HRV at 90 days and 180 days increased significantly compared to the baseline HRV (seven-day) in SDANN, SDNN, LF and HF bands. For patients without thrombolytic therapy, their follow-up HRV at 90-day and 180-day increased significantly as compared to the baseline HRV (seven-day) in SDANN and SDNN only. After correction of ventricular ejection fraction, the higher short-term (seven day) HRV activities were still present in SDANN and SDNN in patients with thrombolysis as compared to those without. The 90-day and 180-day HRV did not differ between patients with and without thrombolytic agent. Three patients died suddenly during follow-up, and all showed significantly lower values of HRV than the survivors. CONCLUSIONS: The findings of the present study suggest that 1) in patients with uncomplicated AMI, HRV was transiently reduced with progressive improvement within three months after AMI in both those with and without thrombolytic therapy, and 2) patients who had received thrombolytic treatment had more improved HRV early (seven days) after AMI than those who did not. This improvement, independent of the change of left ventricular function, could be associated with the beneficial effect of thrombolytic therapy in patients with AMI.