We analyzed the expression of MHC class I (W6/32) and class II (HLA-DR) antigens on human fetal and postnatal thymocytes by fluorescence-activated cell sorting. Less than 5% of prenatal thymocytes expressed HLA-DR before week 12 of gestation. However, the number of HLA-DR-positive cells significantly increased during the late second and third trimester of gestation, when greater than 50% of prenatal thymocytes expressed HLA-DR. Such high-level expressions of HLA-DR in fetal thymocytes were also demonstrated by Northern-blot analysis and immunohistochemistry. After birth, the percentage of HLA-DR-positive cells in thymocytes decreased gradually. A high-level expression of class I antigen was also observed in thymocytes from the early stages of gestation, but, in contrast to MHC class II, a majority of postnatal thymocytes maintained high levels of class I antigen after birth.