We have examined some aspects of lymphocyte and macrophage function in experimental murine amyloidosis. Casein-induced murine amyloidosis is a good model for studying secondary human amyloidosis while myeloma-associated murine amyloidosis is a poor model for human myeloma-associated amyloidosis. The amyloid of casein-induced and myeloma-associated murine amyloidosis cross-reacted immunologically. Neither form of amyloidosis was associated with L chain fragments or excess L chain production. Cellular immunologic reactivity of casein-induced amyloidotic mice, as assessed by lymphocyte transformation with mitogens, was abnormal using spleen lymphocytes but completely normal when thymus and peripheral blood lymphocytes were examined. The depressed activity could be attributed to splenic amyloid deposits. Intracellular amyloid was detected in the spleens of casein-injected mice prior to extracellular amyloid deposits. Amyloid containing cells could also be cultured from the spleen in a much higher proportion than that found in vivo. These cells may represent a subpopulation committed to amyloid synthesis.