To study left ventricular diastolic properties in syndrome X, we analyzed transmitral filling dynamics during handgrip exertion. In 14 normal subjects (N), 17 with syndrome X (Syn X), 16 with single-vessel disease (SVD), and 8 with multiple-vessel disease (MVD), transmitral inflow was recorded at baseline and during handgrip (50% of maximal effort for one minute) using pulsed Doppler echocardiography. We measured early diastolic (E) and late atrial (A) inflow velocities, A/E ratio and percent change of A/E from baseline (%A/E). Blood pressure and heart rate increased to the same degree in each group during handgrip. In normal subjects, E did not change with handgrip; A (51 +/- 10 vs 54 +/- 11 cm/sec, P < 0.05) and A/E (1.16 +/- 0.22 vs 1.25 +/- 0.33, P < 0.05) increased minimally. In Syn X subjects, E decreased (51 +/- 10 vs 38 +/- 10 cm/sec, P < 0.0001), A increased (52 +/- 11 vs 60 +/- 14 cm/sec, P < 0.005), and A/E increased markedly (1.07 +/- 0.31 vs 1.68 +/- 0.51, P < 0.0001). The %A/E in Syn X and MVD were significantly larger than that in SVD and N (Syn X: 58 +/- 29%; MVD: 45 +/- 25%; SVD: 22 +/- 21%; N: 8 +/- 13%). Handgrip-induced changes in diastolic filling in syndrome X and are similar to those in MVD and more marked than in SVD. These changes are consistent with impaired ventricular relaxation and support a generalized left ventricular (LV) abnormality in syndrome X.