In our earlier studies, the natural killer (NK) cell mediated cytotoxicity was found to be impaired in 55% of chronic myeloid leukemia (CML) patients in remission (low NK responders), while the rest exhibited normal range of cytotoxicity (normal NK responders). In the present investigations probable factors contributing to the impaired NK activity of low NK responder CML patients have been analyzed. Peripheral blood lymphocytes (PBL) from both low and normal NK responder CML patients possessed normal percentages of HNK-1+, CD3+ and CD8+ cells. The proportion of HNK-1+ cells and CD8+ cells in low density fractions (LDF) and high density fractions (HDF) respectively of Percoll separated PBL from low and normal NK responder CML patients and healthy donors was comparable. However, the NK activity of LDF cells of low NK responder CML patients was much lower. Also, HDF cells from low NK responder CML patients exhibited a regulatory effect on NK cytotoxicity of PBL from healthy donors. Therefore, it is likely that the presence of suppressor cells and perhaps an intrinsic inability of HNK-1+ cells may together contribute to the impaired NK cytotoxicity of low NK responder CML patients.