To determine possible correlations between the selective loss of HLA-class-l allelic forms on neoplastic cells and their biological-clinical characteristics, 89 squamous-cell carcinomas of the uterine cervix were evaluated immunohistochemically using monomorphic and polymorphic antibodies against HLA-A, -B, and -C molecules and analyzed clinico-pathologically. Four of the carcinomas exhibited a lack of detectable class-l heavy-chain expression associated with β2-microglobulin. In 19 of 42 HLA-A2-positive patients, tumor cells revealed loss of the HLA-A2 allelic product. Loss of HLA-B7 and/or 40 (B7/40) allelic product(s) on tumor cells was observed in 12 of 2S HLA-B7/40-positive cases. These alterations did not correlate with patient age, clinical stage (FIGO) of the disease, histological sub-type (WHO) or depth of cervical invasion. However, a statistically significant correlation was observed between lymph-node metastases and selective loss of HLA-B7/40 allelic produces), but not with HLA-A2 allelic product on cancer cells of the primary lesion. Our results indicate that selective loss of certain HLA-class-l alleles on neoplastic cells can influence the nodal metastatic potential and suggest that these 2 class-l molecules may have different immune functions as restriction elements in T-cell-mediated cytotoxicity.