Abstract. Because of unexplained mortality among 33 sibling offspring of a single pair of dogs, a family of Jack Russell Terriers was investigated. Twelve pups, 5 male and 7 female, died between 8 and 14 weeks of age. Six of those animals died in the field within 50 hours following vaccination with modified live vaccines. Subsequent histopathologic examination revealed the absence of splenic white pulp in 4 dogs and hepatic inclusions diagnostic for adenoviral infection in 2 dogs. Two additional litters yielded 2 pups with the same splenic and hepatic lesions. These observations led to a detailed study of 7 siblings whelped specifically for this investigation. Four of these 7 siblings had a profound lymphopenia and a decrease in serum immunoglobulins. Six of these dogs were necropsied at 7 weeks of age, and 4 of them had marked hypoplasia of all lymphoid tissue. The affected pups had an 86% decrease in mean thymic weight, with poor corticomedullary differentiation, and very few CD3-positive (T cell) thymocytes were detected immunohistochemically. However, the affected thymic tissue stained intensely with a immunochemical stain for cytokeratin. The other affected lymphoid tissues were identified histologically only by stromal architectural characteristics. Lymph nodes lacked both CD3 and CD79a (B cell) positive cells. The analyzed breeding data were consistent with an autosomal recessive mode of inheritance. This canine severe combined immunodeficiency has immunologic and pathologic features similar to those observed in immunodeficient C.B-17 mice and Arabian horses.Severe combined immunodeficiency (SCID) refers to a heterogeneous group of genetic disorders characterized by T-and B-lymphocyte dysfunction often resulting in death during infancy. 2,11 Both autosomal recessive and X chromosome-linked forms (XSCID) have been identified. The XSCID have been associated with mutations in the common gamma subunit of several cytokine receptors and are the most common of the primary immunodeficiencies in human beings and dogs. 2,3,5 In the Basset Hound and Cardigan Welsh Corgi, variable B-cell and decreased T-cell levels in blood are associated with reduced IgG and IgA immunoglobulins and a lack of blastogenic response to T-cell mitogens. 6 Gross pathologic findings in these animals typically include generalized hypoplasia of lymphoid tissues, including the thymus. 14 Autosomal recessive forms of SCID have been described in children, mice, and the Arabian horse 6,13 but not in the dog. In this study, the clinical, immunologic, and pathologic features of a novel canine SCID were examined. Twelve affected individuals were identified among 33 offspring of a single mating pair of Jack Russell Terriers with a defect similar to SCID in mice and horses.