In situ immunophenotypic studies show that tumor infiltrating T lymphocytes from six of 11 fresh cutaneous primary melanomas tested contain T-cell receptor gamma delta expressing cells whereas those from 8 metastatic melanomas did not. In three cases these cells represent an unexpectedly high proportion of the lymphocytic infiltrate, ranging from 15 to 25%. This elevated percentage is maintained when tumor infiltrating lymphocytes are propagated in vitro for 2 or 3 weeks in the presence of recombinant interleukin 2 and autologous tumor cells. Functional studies reveal that gamma delta lines or clones developed from lymphocytes infiltrating primary melanoma display, in addition to their natural killer-like activity, a potent autologous tumor cell cytotoxic activity that does not seem to be restricted by major histocompatibility complex gene products.