We have studied the effect of alkylating agents (AA): cyclophosphamide (Cy), 4-hydroperoxycyclophosphamide (4HCy), mafosfamide (MF), and nitrogranulogen (NTG) on cytotoxicity evaluated in ADCC and NK assays. While NK cells were sensitive to AA, higher concentrations of 4HCy and MF were necessary to affect killer cells active in ADCC assay. NTG which was without any effect on ADCC was found to be the most efficacious inhibitor on NK activity.