Major histocompatibility complex (MHC) class II antigens are expressed on adrenocortical cells of the zona reticularis and have been shown to be a marker of dignity. This suggests a correlation to the zellular differentiation of the adrenal cortex. Therefore, we immunohistochemically investigated the MHC class II expression in the context of the ontogenesis of the zonal and cellular differentiation in fetal, postnatal, childhood, and adult adrenals. Cell types and cell turnover were studied using specific immune markers (including expression of CD95/ Fas), in situ end labeling of apoptosis, and electron microscopy. We show that prenatal (fetal and definitive) steroid cells, as well as postnatal adrenals, reveal no expression of MHC class II. In childhood, these antigens first appear by the fourth year, in parallel with the differentiation of reticularis cells. The expression index in childhood was 7.43% +/- 2.78 (mean +/- SEM), in adult adrenals 18.63% +/- 3.14 (third decade), and 15.15% +/- 1.26 (fourth through sixth decade). In conclusion, MHC class II expression and the development of the functional maturation of the adult adrenal cortex occur simultaneously. The expression of MHC class II on steroid cells may thus be involved in potential immune-adrenal interactions.