The peripheral blood regeneration of natural killer (NK) cells was studied before and on 5 occasions during the first 6 weeks after autologous bone marrow transplantation (auto-BMT) in 10 patients with hematological malignancies and solid tumors. The number of NK cells (relative as well as absolute), enumerated by their lack of CD3 and their expression of CD56 recovered after a severe decline 1 week posttransplant to increase beyond pretransplantation levels during the next 2 weeks. Similar patterns were seen for the average NK activity against K562 as well as LAK cell lytic activity against Daudi but without the overshoot at weeks 2-3. Moreover, the fraction, but not the absolute numbers, of NK cells was found to correlate to the lytic NK activity. In contrast, no phenotypic marker was correlated to LAK activity. Immunophenotypic studies using three-color flow cytometry revealed that during the first 2 weeks after auto-BMT the phenotype of NK cells changed towards an immature phenotype (decreased CD45RA and CD11a) 1 week after transplant to an activated (increase in CD25, HLA-DR and CD11c) after 2-4 weeks. However, when the absolute number of selected phenotypically defined NK cell subsets(CD45RA, CD45RB, CD11a, CD11c, CD2, CD25, HLA-DR and fibronectin expressing CD56+,CD3- NK cells) were compared to the cytotoxic activity for each patient, we were not able to show any correlations except between the activation-related antigens CD25 and HLA-DR on the one hand, and NK lysis on the other, and only 3 weeks after auto-BMT. We conclude that NK cell function recovers quickly following auto-BMT concomitantly with the emergence of a transiently altered phenotype which increased expression of activation-related antigens.