A role for naturally occurring cytotoxic cells in immunosurveillance against malignancy has been presumed in several studies. The natural killer activity (NKA) of peripheral blood mononuclear cells was therefore measured at regular intervals in patients with acute leukaemia and expressed specific cytotoxicity. Sixty controls had a median NKA of 33·6% (range 15·4–71). Seventy-three patients with acute lymphoblastic leukaemia (ALL) and acute non-lymphoblastic leukaemia (ANLL) with untreated or relapsed disease had a median activity of 2·4% (range 0–13·4) (P< 0·001), while 57 patients who had achieved complete remission had a median activity of 22·7% (range 9·5–64·4). In 15 patients, reductions of NKA were seen prior to 16 episodes of relapse. In ten of these (nine with ANLL and one with ALL), 11 relapses were preceded within 10 weeks by drops in NKA to less than 30% of remission levels. The median NKA of the group prior to the drop in activity was 25·5% and the median first low value was 60%. Five patients who relapsed after allogeneic bone marrow transplantation had significant, sustained drops in NKA, 5–9 weeks earlier. The median NKA prior to the drop was 25·6% and the median first low value was 8·0%. We therefore conclude that there was a marked reduction in NKA in patients with active acute leukaemia when compared with healthy blood donors and that this activity substantially improved in complete remission. All patients who relapsed had significantly reduced NKA which in some, significantly preceded the time of relapse. These data suggest that the regular assessment of NKA in patients with acute leukaemia may be a useful diagnostic tool.