This paper reviews recent publications and presents data dealing with natural killer (NK) cell activity in the tumor-infiltrating lymphocytes (TIL) and peripheral blood (PBL) of patients with solid tumors and leukemia. Cells with NK markers or function are not a prominent feature of lymphoid infiltrates in solid tumors and, when present, do not appear to correlate with other prognostic variables. Nevertheless, NK cells among IL-2-activated TIL mediate antitumor cytotoxicity. Many studies indicate that NK activity is reduced in patients with advanced cancer. In some of these studies, low NK activity has been shown to be an unfavorable prognostic variable. PBL, splenic and bone marrow NK activity in patients with acute myelogenous leukemia (AML) is also decreased. However, adherent IL-2-activated lymphocytes composed primarily of NK cells were found to be cytotoxic against AML blasts and could be generated from patients in remission and relapse. The question of whether low NK activity in solid tumors and leukemia is the result of the disease state or contributes to it, remains unanswered. Data are also presented here showing that treated, apparently disease-free patients with high PBL NK activity have a significantly longer metastasis-free survival time than those with low NK activity (n= 91, p< 0.026, Cox proportional hazards test).