Major histocompatibility complex (HLA system) class II molecules including HLA-DR antigens, associate with peptides, which are derived from antigens, for presentation to T4 lymphocytes. Functional and adhesion assays have shown that CD4 molecule interacts with HLA class II molecules, leading to enhanced responses of T4 cells. In the present study, we examined the tissue expression of HLA-DR antigens and the quantitative variance of T4 lymphocytes in a series of 50 "endometrioid" adenocarcinomas of the endometrium and 35 cervical squamous-cell carcinomas. A three-step avidin-biotin immunoperoxidase staining method was applied. As primary antibodies, we used the TAL.1BS monoclonal antihuman HLA-DR alpha (alpha) chain antibody and the OPD4 mouse antihuman antibody; the latter mainly identifies benign T4 lymphocytes. Twenty-four percent (24%) of women with endometrial cancer were high immune responders, while the relative percentage in women with cervical cancer was 40%; the respective tumours were of early clinical and surgical stages. HLA-DR determinants were predominantly expressed in membranes of stromal cells, mainly histiocytes, usually around HLA-DR+ lymphoid cells, as well as on endothelial cells. Greater numbers of OPD4+ aggregated lymphocytes were observed when the tumour stroma was rich in HLA-DR+ cells. Epithelial elements, either cancerous or benign, were seldom HLA-DR+. In those samples, positive immunolabelling was often confined in the intercellular space and did not seem to activate an effective host immune response against neoplastic cells. High expression of HLA-DR molecules in professional antigen presenting stromal cells may be used as a lymphocyte activation marker in endometrial and cervical carcinomas. This activation appears to be an early event in the evolution of invasive endometrial and cervical carcinomas.