To determine left ventricular diastolic properties in patients with familial amyloid polyneuropathy, 23 patients were studied by digitized M-mode echocardiography and were compared with 15 age-matched normal subjects. None of the patients had restrictive ventricular physiology and all but two showed normal left ventricular fractional shortening. Both the normalized peak rate of diastolic increase in left ventricular internal dimension and the normalized peak rate of diastolic thinning of posterior wall were significantly lower in patients than in normal subjects (2.0 +/- 0.8 vs 3.0 +/- 0.4 sec-1; p less than 0.001, and 2.5 +/- 1.2 vs 5.8 +/- 1.0 sec-1; p less than 0.001, respectively). The left ventricular isovolumic relaxation time in patients was 91.5 +/- 22.2 msec, compared with 64.0 +/- 2.6 msec in normal subjects (p less than 0.001). Of the 18 patients without clinical evidence of overt heart disease, 12 had normal ventricular wall thickness and normal fractional shortening, but 10 of the 12 exhibited some abnormalities in diastolic properties. In addition, indexes of diastolic function were significantly related to ventricular wall thickness alone. These findings indicate that left ventricular diastolic abnormalities precede the development of clinically overt heart disease, ventricular wall thickening, and systolic dysfunction and may be related to intramyocardial amyloid infiltration with resultant fibrosis in patients with familial amyloid polyneuropathy.