Recovery of natural killer (NK) cells after cessation of chemotherapy for childhood acute lymphoblastic leukemia (ALL) and solid tumors was investigated in 25 children aged 3 to 18 years. The numbers of CD3-CD56+, CD16+, and CD8-CD57+ cells in peripheral blood were analyzed with monoclonal antibodies and flow cytometry at 0, 1, 3, 6, 9, and 12 months after discontinuation of therapy. The CD3-CD56+ and CD16+ cell counts of ALL patients (n = 14) were below the mean -1 SD values of controls at cessation but normalized within one month due to a rapid 2.1 and 4.5 fold increase, respectively. The CD8-CD57+ cell count of ALL patients was normal compared to controls at cessation. In solid tumor patients (n = 11), the counts of all NK cell phenotypes studied were of normal amount compared to controls at cessation and no vigorous increase occurred after the therapy. NK cell function was determined by killing K 562 target cells in five patients. In the two standard risk ALL patients tested, the activity was still low at 5 months after therapy. In contrast, the function was normal at 1 month (Wilms' tumor), 3 months (Mb Hodgkin's) and 6 months (Burkitt lymphoma). In conclusion, NK cell counts were decreased compared to controls during therapy for ALL, but recovered rapidly afterwards. In spite of normal counts, NK cell function may be impaired for several months. The number and function of NK cells is less affected in solid tumor patients. These differences may reflect the milder immunosuppressive effect of interval cytostatic medication in solid tumor patients when compared to the more intensive continuous therapy in ALL patients.