Experimental autoimmune thyroiditis was induced in transgenic mice (TG-3) producing human α-fetoprotein (AFP) and in control mice by immunization of porcine thyroid peroxidase (TPO). Development of thyroiditis accompanied with mononuclear cell infiltration was observed in 6 out of 8 treated control mice. In contrast, the development was significantly suppressed in TG-3 mice and mild histologic change was observed in only 1 out of 8 TG-3 mice (p < 0.05). Serum anti-TPO antibody titers gradually increased in TG-3 mice as well as in control mice and there were no significant differences. In vitro phytohemagglutinin response of splenocytes from TG-3 mice was lower than that from control mice. Significantly reduced numbers of CD4+ and CD8+ splenocytes, total thymocytes, and CD4+ thymocytes were found in the nontreated TG-3 mice as compared with those in control mice. These results suggest that ubiquitously produced AFP modulates in vivo T cell development and/or T cell-dependent immune responses.