To investigate ventricular long-axis function in cardiac amyloidosis (CA) and idiopathic restrictive cardiomyopathy (IRC), 16 patients with CA and 14 with IRC were studied. Left ventricular (LV) long-axis function was depressed in all patients with CA compared with only 36% of patients with IRC. Impairment in longitudinal function was clearly evident, even if fractional shortening and LV filling were normal. Ventricular long-axis function may be used as a sensitive marker of early systolic dysfunction. CA and IRC have quite distinct pathophysiologic profiles, raising some concerns about the appropriateness of considering them as 2 subtypes of a single nosographic entity.