One hundred and thirty-six cardiac valves obtained surgically from 124 patients (aged 15-77 years) were examined. Microdeposition of amyloid was present in sclerotic or sclerocalcific lesions of aortic valves in 38 out of 75 (51%) and mitral valves in 21 out of 61 (34%). Amyloid deposition was not significantly related to the age of the patients. An antiserum raised against a low molecular weight protein extracted from amyloid-laden valvular tissues (about 20 g) reacted positively to amyloid in the cardiac valves. It did not react to amyloid deposition containing fibril proteins including light chain related amyloidosis, reactive amyloidosis, systemic senile amyloidosis, isolated atrial amyloidosis, beta-2-microglobulin related amyloidosis and beta protein related amyloidosis. Further, amyloid in the cardiac valves failed to react immunohistochemically to anti-AA, anti-AL, anti-TTR, anti-ANF, anti-beta 2M and anti-beta protein antibodies. These findings suggest that an unknown amyloid protein is involved in the damaged valves.