Thirty patients with primary amyloidosis in whom cardiac involvement was suspected underwent endomyocardial biopsies. Medical records and biopsies were reviewed and echocardiograms were interpreted by observers who were unaware of the recorded findings. Cardiac amyloidosis was documented by endomyocardial biopsy in 30 (100%) of the patients. In two patients, amyloid was present in only one of four specimens, suggesting that a minimum of four biopsy samples is necessary to eliminate the possibility of sampling error. Only 36 (55%) of 65 biopsy specimens of extracardiac tissues contained amyloid. Findings were positive for amyloidosis in 11 (58%) of 19 rectal biopsies and in 16 (52%) of 31 bone marrow biopsies. Of interest, only the endomyocardial biopsy tissues were positive for amyloid in eight (27%) of the 30 patients, among whom 12 extracardiac biopsies had been performed. Two-dimensional echocardiography was consistent with the diagnosis of amyloidosis in 19 (68%) of 28 patients and was abnormal but nonspecific in the remainder. Endomyocardial biopsy frequently provides information about cardiac involvement with amyloid when biopsy of other organs is negative or echocardiography is nonspecific.