Loss of expression of blood group antigen H is associated with cellular invasion and spread of oral squamous cell carcinomas. Membrane-bound carbohydrates may influence the metastatic behavior of cancer cells. Forty-two squamous cell carcinomas (SCC) of the buccal and maxillary alveolar mucosa were studied retrospectively using a monoclonal antibody (BE2) that reacts with blood group H (type 2 chain) structure and an immunoperoxidase (avidin-biotin peroxidase complex) staining technique. H-antigen staining within the entire tumor did not correlate with the stage of the tumor, i.e., tumor spread. However, loss of staining within the most invasive sites of the tumors correlated significantly with the stage of tumor development and histologic grade of malignancy. These findings support the view that features regarding the cells of deeper parts of the carcinomas are very important for the clinical behavior of the tumors and that loss of H-antigen expression is related to the stage of the tumor and invasion of carcinoma cells. 