Natural killer (NK) cell numbers and lytic activity were determined in 40 children with various types of solid malignant neoplasias and in 25 control children by NKH-1 monoclonal antibody and cytotoxicity against K562 target cells, respectively. Patients were analyzed at the time of diagnosis before initiation of therapy and followed over a median time of 15.8 months. Mean NK cell numbers and lytic activity were similar among different types of tumor analyzed. Patients with localized disease (stages I, II; n = 25) also showed values not statistically different from those of patients in advanced disease (stages III, IV; n = 15). According to their response to therapy, patients were divided into three groups: group 1 (complete remission; n = 28), group 2 (partial remission; n = 5), and group 3 (progression of disease; n = 6). Patients in group 3 showed at the time of diagnosis a mean NK activity significantly lower than that of patients in groups 1 and 2 and control children (P = 0.007). The defect in NK cell lytic capacity in vitro observed in patients with progressive disease suggests that NK cells play a role in the control of neoplastic growth in vivo and may imply that some children with refractory progressive disease can benefit from immunomodulation destined to improve the lytic potential of NK cells.