INTRODUCTION: Inflammation has a major role in atherosclerosis and the acute phase C-reactive protein (CRP) is elevated after acute myocardial infarction. Inflammation is also implicated in autonomic nervous system control. Heart rate variability (HRV) has been used as a marker of abnormal autonomic activity after myocardial infarction. Our purpose was to investigate the relation between CRP levels and autonomic tone in patients after acute ST-segment elevation myocardial infarction. METHODS: We studied prospectively 98 patients. CRP and the cardiac enzymes CK, CK-MB, and troponin-I were measured for a total of 72 hours and 24-hour Holter ECG recordings for HRV analysis were acquired before hospital discharge. RESULTS: The natural logarithm of CRP levels was inversely correlated with the following logarithmic transformed indices of HRV in the time and in the frequency domain: SDNN, standard deviation of all normal R-R intervals, (r = -0.40, p < 0.001); SDANN index, standard deviation of the average normal R-R intervals for 5-minute segments, (r = -0.46, p < 0.001); SDNN index, mean of the standard deviation of all normal R-R intervals for 5-minute segments (r = -0.41, p < 0.001); total power (TP) (r = -0.38, p < 0.001); high frequency power (HF) (r = -0.31, p < 0.01); low frequency power (LF) (r = -0.45, p < 0.001). The strong inverse relation between CRP and SDNN, SDANN, SDNN index, LF and TP persisted after adjustment for left ventricular function. CONCLUSIONS: Increased levels of circulating CRP after acute myocardial infarction are associated with attenuated HRV indices, suggesting a possible relationship between inflammation and cardiac autonomic balance.