Cardiovascular diseases are the main cause of death in Mexico City and have shown a rising trend over the past 20 years. Various epidemiological studies have reported an association between respirable particles and carbon monoxide (CO), with cardiorespiratory outcomes. The purpose of this study was to assess the effect of particulate matter with aerodynamic diameters of less than 2.5 microm (PM(2.5)), also known as respirable or fine particles and CO on heart rate variability (HRV) in 5-min periods in patients with known ischemic heart disease. 30 patients were selected from the outpatient clinic of the National Institute of Cardiology of Mexico and followed during 11 h, using electrocardiography (ECG) ambulatory electrocardiograms and personal monitors for CO and PM(2.5). We calculated frequency-domain measurements using power spectral analysis and assessed the association with pollutants using mixed models analysis in 5-min periods. We found a decrease in HRV measured as high frequency (Ln) (coefficient=-0.008, 95% confidence interval (CI), -0.015, 0.0004) for each 10 microg/m(3) (micrograms per cubic meter) increase of personal PM(2.5) exposure. We also found a decrease of low (ln) (coefficient=-0.024, 95% CI, -0.041, -0.007) and very low frequencies (ln) (coefficient=-0.034, 95% CI, -0.061, -0.007) for 1 parts per million (p.p.m.) increase in CO personal exposure after adjustment for potential confounding factors. These results show that for this high-risk population, the alteration of the cardiac autonomic regulation was significantly associated with both PM(2.5) and CO personal exposures.