The immunologic status, occurrence of autoantibodies, and serum abnormalities in relation to age increase and pathologic changes were investigated in SJL/J mice. The Immunologic reactivity of normal SJL/J mice and those with spontaneous reticulum-cell tumors was evaluated with age increase. Tested were the response to sheep red blood cells, prolongation of skin allograft survival, delayed hypersensitivity skin reaction, and graft-versus-host reaction. The immune reactivity decreased as the mice grew older, whether the host was normal or tumor bearing. This defective immunologic status early in life did not seem, therefore, to be a factor in the spontaneous tumor development. Antibodies to nuclear material were detectable in normal animals as early as 3 months and increased with age in normal animals, but were significantly less common in tumor-bearing animals. Direct antiglobulin tests (Coombs') on blood samples taken from animals ranging from 6 to 14 months of age were negative. Serial serum electrophoresis showed the presence of proteins, sometimes myeloma-like, with restricted heterogeneity, always associated with mainly early tumors in 6- to 10-month-old mice, and an abundance of plasma cells.