Fifty male and 49 female B6;129 mice (wild-type, + / + ) were maintained until 2 years of age to study their age-related pathology. By 104—105 weeks, 14/50 (28%) of the males and 30/49 (61%) of the females were still alive. The most common contributing cause of morbidity or mortality was lymphoma. Lymphoma was observed in 21/50 (42%) of the males and 33/49 (67%) of the females with the most common sites being mesenteric lymph nodes, gut associated lymphoid tissue (Peyer's patches), and spleen. The lymphoma most often appeared to arise in the mesenteric node. Immunohistochemistry revealed CD45R expression as well as infiltration by many CD3+ T cells. IgH gene rearrangements were found in typical mesenteric node lymphomas indicating B-cell origin. They bore similarities to the human T-cell rich, B-cell lymphomas. Other tumors included hepatocellular adenoma or carcinoma (male 12%, females 10%), lung alveolar Type II cell adenoma or carcinoma (male 32%, female 20%), thyroid follicular adenoma or carcinoma (male 2%, female 8%), ovarian tumors (17%), and endometrial tumors (6%). Nonneoplastic lesions included amyloidlike material in the nasal septum (male and female 100%), otitis media (male 84%, female 79%), epididymal epithelial karyomegaly (88%), melanosis (high incidences in various tissues including brain, parathyroid, and spleen), membranoproliferative glomerulonephritis (male 52%, female 71%), hyalinosis with extracellular crystals in several tissues (respiratory tract, gall bladder, stomach), islet cell hyperplasia (male 45%, female 29%) and esophageal dilation (male 10%, female 6%). The B6;129 mouse is a mouse with aging lesions similar to those in other mouse strains but with a characteristic common lymphoma.