NZB and (NZB × NZW) F1 hybrid mice are a widely studied model of several, sometimes clinically related, human diseases of unknown etiology. These diseases include idiopathic glomerulonephritis, systemic lupus erythematosus, related connective-tissue and autoimmune diseases, and malignant lymphoma. Our work on the animal model reveals interrelated viral (Gross leukemia virus), genetic, and immunologic determinants of disease. These studies may contribute to the further elucidation of the cause, nature, treatment, and prevention of one or more of the corresponding human diseases.