We examined tumor infiltrating leukocytes (TIL) in frozen sections of 28 biopsies from squamous cell carcinomas of the head and neck (SCCHN). In so doing, we used monoclonal antibodies (MoAb) directed against various leukocyte antigens. As defined by HLe-1+ cells, leukocyte infiltration was present in all biopsies. The amount of HLe-1+ cells was more often greater in stage III than in stage IV lesions. Most of the TIL were identified as CD5+ T-lymphocytes. In contrast, CD19+ B-cells were sparse in most biopsies. CD14+ monocytes/macrophages were found in only a few specimens. The relative proportion of CD4+ T-helper cells was higher than or at least equal to CD8+ suppressor/cytotoxic cells in all samples tested. Interleukin-2 (IL-2) receptor+ lymphocytes were evident in 13 of 22 biopsies stained for CD25 reactivity, and were more often observed in stage III than in stage IV tumors. All biopsies from recurrent tumors had no detectable IL-2 receptor+ cells. Our findings provide evidence for a positive correlation between a greater amount of TIL in earlier stages of SCCHN. The presence of IL-2+ lymphocytes suggests that SCCHN may be capable of activating resting lymphocytes for further IL-2-induced proliferation.