Blasts from patients with untreated acute lymphocytic leukemia (ALL) were examined for their natural killer (NK) and antibody dependent cellular cytotoxicity (ADCC); lectin dependent cellular cytotoxicity (LDCC); capacity to suppress cytotoxicity of normal lymphocytes and ability to produce interferon (IF) in vitro. For the NK assay, K562 and CEM cell lines were used as targets; in the ADCC assay, antibody coated SB cells were used. Lymphocytes from ALL patients demonstrated no NK or ADCC activities at various effector to target cell ratios and showed negligible LDCC activity against SB targets when compared to normal donors. Leukemic lymphocytes precultured with Con A for 72 hr did not suppress the NK activity of normal effector cells in comparison to significant suppression produced by normal lymphocytes precultured with Con A. Supernates from leukemic cells caused enhancement of NK activity of normal lymphocytes contrasted to significant suppression of NK activity produced by supernates from normal lymphocytes. Further, the ability of leukemic lymphocytes to produce IF in response to K562 and SB target cells in vitro was also minimal. These results demonstrate that defective immunoregulatory mechanism may be responsible for failure of the immune surveillance mechanism to prevent growth of leukemic cells.