Chronic energy-intake restriction (CEIR) has been shown to increase life-span, delay diseases expression, and inhibit immunological perturbations in all strains of autoimmunity-prone mice studied, including NZB, (NZB x NZW)F1, MRL/Mp-lpr/lpr, BXSB, and kd/kd mice. In (NZB x NZB)F1 mice, increased percentages and increased absolute numbers of Ly-1+ B lymphocytes in spleen, mesenteric lymph nodes, thymus, and bone marrow as revealed by two-color immunofluorescence analysis were greatly reduced by CEIR with a diet high in carbohydrate and low in fat. This influence on a possibly crucial lymphocyte subpopulation was associated with delayed onset of disease and with greatly prolonged life-span. In the present investigation, the percentages and absolute number of Ly-1+ B lymphocytes in the spleen, peritoneal exudate, and peripheral blood were found to be increased in each autoimmunity-prone strain studied. CEIR decreased the absolute and relative numbers of the Ly-1+ B lymphocytes in mice of each of the autoimmunity-prone strains and returned the number and proportions of Ly-1+ B cells close to levels present in the same locations in genetically long-lived C57BL/6, DBA/2, or BALB/c mice fed a standard commercial diet ad libitum.