This study reports the effects in vitro and in vivo of L-canavanine (LCN), an amino acid found in commonly consumed legumes, on immune function in normal and autoimmune mice. L-Canavanine in high doses effectively blocks all DNA synthesis in vitro within 24 h. At lower doses, LCN affects B-cell function of autoimmune New Zealand Black/New Zealand White (NZB/NZW)F₁ mice, inhibiting [³H]thymidine incorporation in response to B-cell mitogens, and pokeweed-induced intracytoplasmic immunoglobulin synthesis. LCN stimulates intracytoplasmic immunoglobulin (IgG > IgM). T-cell functions such as lymphoproliferation in response to concanavalin A or phytohemagglutinin and T-cell cytotoxicity are not affected. Suppression of the lipopolysaccharide response by LCN is removed by the addition of fresh B cells. Addition of the amino acid to mouse diet resulted in a decrease in the life-span of the autoimmune NZB and (NZB × NZW)F₁ mice and abolished the protective effect of male sex on their survival. The decrease in survival in LCN-treated autoimmune mice correlated with an increase in spontaneous immnunoglobulin-secreting cells (IgG > IgM) and antinuclear and double-stranded DNA antibodies. The histopathological analyses revealed increased glomerular damage and immunoglobulin deposition in the kidneys of the LCN-treated autoimmune and normal (DBA/2) mice. Ten percent of normal mice developed high titers of autoantibodies after 24 weeks of the diet. These data suggest a dietary amino acid, L-canavanine, affects B-cell function resulting in autoimmune phenomena and providing a new animal model of autoimmunity, a diet-induced systemic lupus erythematosus.