The mechanism by which GVHD augments the graft-versus-leukemia (GVL) effect of marrow transplants has not been ascertained. One possibility involves the secondary activation of natural killer (NK) cells by cytokines released during the GVHD process. To evaluate this possibility we have compared NK activity and lymphokine-activated killer cell precursor (LAKp) frequencies in serially sampled PBMC from recipients of unmanipulated autologous or allogeneic marrow with and without active GVHD. NK activity recovered rapidly after BMT and was elevated during episodes of acute GVHD. However, NK activity did not differ between recipients of autologous or allogeneic marrow without GVHD nor was NK activity increased in association with chronic GVHD. Endogenously-activated NK cells were detected only in recipients of allogeneic marrow but this did not correlate with GVHD status. In contrast to NK activity, LAKp frequencies fell below the control range during the first 8 weeks after BMT. By 9-14 weeks the median LAKp frequency was normal and did not differ between the three groups then or later after transplant. We conclude that acute GVHD may serve to increase the lytic activity of NK cells but does not result in increased LAKp. LAKp frequencies are below normal during the first two months after BMT, a finding not previously recognized from bulk culture LAK studies. The role of LAK effectors in GVL may involve more the degree of cellular activation rather than the number of cells activated.