This study investigated the effect of dynamic exercise on mitral regurgitation (MR) as assessed by color flow Doppler imaging and tested the hypothesis that MR increases in patients with left ventricular (LV) function worsening during exercise. We studied 513 patients (390 men, 123 women:mean age [+/-1 SD] 58+/-11 years) referred for treadmill exercise echocardiography (EE) to evaluate known or suspected coronary artery disease. Normal EE was seen in 182 (36%), necrosis in 131 (25%), and ischemic response (with or without necrosis) in 200 (39%). MR assessment was performed at rest and immediately postexercise, on the basis of the mosaic area. At rest, mild MR (<3 cm2) was seen in 138; moderate (3 to 6 cm2) was seen in 21; and severe (>6 cm2) was seen in 5. Forty-two patients developed new, mild (n=35), moderate (n=6), or severe (n=1) MR during exercise. Patients were assigned to three groups: group 1--new or increased MR from rest to exercise (n=70); group 2--MR at rest unchanged or decreased (n=136); and group 3--no MR at rest and exercise (n=307). At rest, LV ejection fraction (EF) and wall motion score index (WMSI) were similar in group 1 and group 2 but improved in group 3 (EF: group 1, 51+/-11%; group 2, 53+/-10%; group 3, 56+/-8%, p<0.001 vs group 1 and group 2. WMSI: group 1, 1.3+/-0.3; group 2, 1.3+/-0.4; group 3, 1.1+/-0.2, p<0.01 vs group 1, p<0.001 vs group 2). At exercise, EF and WMSI were impaired in group 1 (EF: group 1, 52+/-14%; group 2, 58+/-15%; group 3, 64+/-11%, p<0.001 vs group 1 and group 2; p<0.05 between group 1 and group 2. WMSI: group 1, 1.5+/-0.4; group 2, 1.4+/-0.4; group 3, 1.2+/-0.3, p<0.001 vs group 1 and group 2, p<0.05 between group 1 and group 2). An ischemic response was common in group 1 (67% vs 35% in group 2 and 34% in group 3, p<0.001 between group 1 and group 3 and between group 1 and group 2). Accordingly, in group 1 patients, exercise time was diminished (7.3+/-2.7 vs 8.4+/-2.7 in group 2 and 9.3+/-2.4 in group 3, p<0.01, between group 1 and group 2, p<0.001 between group 1 and group 3, p<0.001 between group 2 and group 3) and the number of severely narrowed coronary vessels greater (2.4+/-0.9 vs 1.7+/-1.0 in group 2 and 1.7+/-1.0 in group 3). In conclusion, MR does not increase in most patients submitted to dynamic exercise echocardiography. However, if MR develops, severe LV function worsening should be suspected.