CONTEXT: Epidemiological studies have shown an association between the incidence of adverse cardiovascular effects and exposure to ambient particulate matter (PM). Diesel exhaust (DE) is a major contributor to ambient PM and gaseous emissions in urban areas. OBJECTIVE: This was a pilot study designed to evaluate concentration-dependent effects of short-term exposure to whole DE on the cardiovascular system in order to identify a threshold concentration that can elicit biological responses in healthy human volunteers. MATERIALS AND METHODS: Six healthy middle-aged participants with glutathione-S-transferase-Mu 1 (GSTM1) null genotype underwent sequential exposures to 100 microg/m(3), 200 microg/m(3), and 300 microg/m(3) whole DE generated in real time using an idling diesel truck engine. Exposures were separated by 14 d and each was 2 h in duration. RESULTS: We report concentration-dependent effects of exposure to DE, with 100 microg/m(3) concentration causing minimal cardiovascular effects, while exposure to 300 microg/m(3) DE for 2 h resulted in a borderline significant reduction of baseline brachial artery diameter (3.34 +/- 0.27 mm pre- versus 3.23 +/- 0.25 mm post-exposure; p = 0.08). Exposure to the highest concentration of DE also resulted in increases of 5 mmHg in diastolic blood pressure as well as a decrease in indices of the frequency domain of heart rate variability (HRV). DISCUSSION AND CONCLUSIONS: These findings demonstrate that acute exposure to relatively high concentrations of DE produces cardiovascular changes in middle-aged GSTM1 null individuals. This study therefore suggests that arterial vasoconstriction and changes in HRV are responses through which traffic-related air pollution increases the risk of adverse cardiovascular outcomes.