The expression of human leukocyte antigen (HLA) class I and class II molecules and one trophoblast-lymphocyte crossreactive (TLX) antigen by human oocytes and granulosa cells was investigated. Well-defined monoclonal antibodies directed against HLA class I and class II molecules as well as beta 2-microglobulin and a TLX molecule were used in a standard indirect immunofluorescence test and some immunogold techniques at the electron microscopic level. Single unfertilizable or multiply fertilized oocytes and granulosa cells obtained from an in-vitro fertilization programme as well as oocytes in primary, secondary and tertiary follicles of ovaries were studied. Neither HLA class I or class II molecules, nor beta 2-microglobulin, nor a TLX molecule were detected on cultured oocytes or oocytes in human ovarian follicles or in their zona pellucida. Granulosa cells taken from a culture medium and those in follicles at various stages of development expressed class I antigens, while granulosa cells from tertiary follicles also expressed HLA-DR antigens. These results confirm that the female human gamete belongs to that very small group of cells that lack major histocompatibility complex antigens. Since spermatozoa also lack HLA antigens, human germ cells are entirely different from other nucleated human cells with regard to the antigenic structures expressed on the cell surface. This would prevent recognition of these cells by the cellular immune system. Furthermore, HLA and TLX antigens are not involved in fertilization and early differentiation.