Of a number of strains of mice studied for evidence of autoimmunity, NZY/B1 mice showed the highest frequency of degenerative arthritis of the knee, reaching a maximum of 68% at 18 months. 50% PN mice were affected at 24 months. Both breeds differed from previously described strains in not showing a sex difference. The NZB/B1 mice were rarely affected and hybrids to the NZY and the backcross to the NZB showed a recessive pattern of inheritance for knee arthritis and an additive pattern for carpal arthritis. Polygenic inheritance was postulated as at least three genes would be necessary to explain the findings. Joint disease was not related to red cell and nuclear antibodies, glomerulitis, or arteritis.