During a 1-year period, 28 animals from a breeding colony of N:NIH(S)-bg-nu-xid mice were discovered to have rapidly enlarging subcutaneous swellings in the ventral, cervical, and axillary regions. Five of the mice also had hind limb paresis. Twenty-two of the mice were heterozygous nude females, five were homozygous nude males, and one was a homozygous nude female. All of the above mice were homo- or hemizygous for the beige and X-linked immunodeficiency mutations. The average age of the mice was 8.3 months. Generalized enlargement of the peripheral and internal lymph nodes was present at the time of necropsy examination. Other lesions commonly noted at necropsy included splenomegaly (15 mice), pale and thickened ventral lumbar spinal musculature (11 mice), and opaque, thickened meninges of the brain (10 mice). Histologic examination consistently disclosed infiltrates of neoplastic lymphoblasts in multiple tissues including lymph nodes, spleen, bone marrow, and meninges of the brain and spinal cord. The cells were positive for IgG on immunofluorescent staining, suggesting that the tumors were of B cell origin. The neoplasms observed in these mice have several similarities to tumors found in immunodeficient humans, suggesting that these mice may serve as useful animal models of lymphoma.