In 28 chronic smokers (11 women, 17 men, 53 +/- 10 years old) with coronary artery disease (greater than 75% stenosis), left ventricular (LV) relaxation and filling behavior was assessed before and after inhalation of 0.9 mg nicotine (1 cigarette) by echocardiography. The following acute nicotine-mediated changes were noted (one-sided Wilcoxon test): heart rate increased from 67 to 81 beats/min (p greater than .001); the early diastolic flow (E wave) integral decreased from 49 to 39 mm (p less than .001); the late diastolic flow integral (A wave) increased from 36 to 41 mm (p less than .01). Consecutively, the ratio between E and A wave flow integrals decreased from 1.4 to 0.9 (p less than .001); the atrial contribution to LV filling rose from 42 to 53% (p less than .001); and the isovolumetric relaxation period increased from 89 to 122 ms (p less than .001). In cigarette smokers with coronary artery disease acute administration of nicotine hence causes a shift of mitral blood flow from early (E wave) to late (A wave) diastole and a prolongation of the isovolumetric relaxation time. Thus, cigarette smoking significantly affects LV diastolic function independently of its role as a risk factor for coronary atherosclerosis.