A patient with asymptomatic primary systemic amyloidosis was studied over a one year period. Results of this investigation demonstrated chemical abnormalities consisting of elevations in sedimentation rate, C-reactive protein, serum hexosamine, and serum globulins, including alpha2, beta, and gamma globulin fractions. Liver biopsy demonstrated parenchymal involvement where amyloid was confined to portal areas and around central veins, without coexisting sinusoidal involvement. This topographic distribution was not found in 30 other patients with either primary or secondary parenchymal hepatic amyloidosis reviewed at this hospital. Renal glomerular amyloidosis was demonstrated by kidney biopsy, despite the absence of albuminuria, and contrasts with its presence in 68 of 69 patients reviewed with histologically proven renal glomerular amyloidosis. Immunohistochemical analyses of the hepatic and renal specimens studied by the Coons fluorescent technique demonstrated human globulin to be present in amyloid deposits in this patient and in five others with secondary amyloidosis. An immunohistologic complement fixation test showed that the hepatic and renal amyloid deposits did not fix guinea pig complement, and this contrasted with fixation of complement in the five patients with secondary amyloidosis. The latter immunohistologic findings raise the possibility that amyloid in this patient with primary amyloid disease may be different patho-genetically and in composition from amyloid in patients with secondary amyloidosis. Further observations with regard to pathogenesis are discussed.