Non obese diabetic (NOD) mice spontaneously develop thyroiditis in addition to diabetes. Mononuclear cells begin to infiltrate the thyroid of these animals in the first month of life. The expression of major histocompatibility complex (MHC) class II (la) antigens by cells in the thyroid from NOD mice of various ages with and without thyroiditis was examined. We found that only 1 of the 9 infiltrated thyroids from 18 8-33 day old NOD mice surveyed expressed MHC class II antigens. Therefore la antigen expression appears to be secondary to infiltration and does not initiate the autoimmune process. Fourteen of 17 (82.2%) infiltrated and 7 of 11 (63.6%) uninfiltrated thyroids from NOD mice aged 51-73 days contained cells expressing la antigens. Sixteen of 18 (88.9%) infiltrated and all 7 of the uninfiltrated thyroids from mice aged>89 days contained la positive cells. These MHC class II expressing cells included thyroid epithelial cells (TEC), as well as interstitial cells such as macrophages. la positive cells in the thyroid have the potential of presenting thyroid specific antigen to infiltrating T cells and thereby maintaining or potentiating thyroid autoimmune destruction. Macrophages were observed in thyroid tissue from 9 of 11 (81.8%) infiltrated and 12 of 15 (80%) uninfiltrated 8-33 day old NOD mice, thyroids from 11 of 16 (68.7%) infiltrated and 6 of 9 (66.7%) uninfiltrated 51-73 day old NOD mice, as well as 28 of 29 (96.5%) uninfiltrated and all 9 of the uninfiltrated thyroid from NOD mice aged>89 days. Thyroids from control age matched non autoimmune BALB/c mice were consistently la antigen negative while macrophages were seen in some of the animals aged>60 days.