The detection of pharmaceuticals in water and wastewater has triggered human and ecological health concerns. As highly toxic compounds, chemotherapy agents (CM), such as the cyclophosphamide (CYP) and ifosfamide (IFO) structural isomers, represent a unique threat. This research elucidated the fate of CYP and IFO during ozonation and advanced oxidation by hydroxyl radicals (HO center dot). Novel semi-batch reactors were used to determine the second-order rate constants for CYP and IFO with O-3 and HO center dot. These reactors provided independent control of the oxidant exposure through continuous and constant aqueous ozone and peroxone (O-3-H2O2) addition. The rate constants for transformation of CYP and IFO by ozone were 2.58 +/- 0.40 M(-1)s(-1) and 6.95 +/- 0.21 M(-1)s(-1), respectively, indicating that ozone alone is not suitable for treating CAs. Transformation of CYP and IFO by hydroxyl radicals was fast, with rate constants of 2.69(+/- 0.17) x 10(9) M(-1)s(-1) and 2.73(+/- 0.16) x 10(9) M(-1)s(-1), respectively. The major transformation products formed by O-3 and HO center dot attack consisted of the 4-hydroxy-, 4-keto-, dechloroethyl-, and imino-derivatives of CYP and IFO. Low yields of the active metabolites of the CM, namely phosphoramide mustard and isophosphoramide mustard, were detected. These findings suggest that treated water may retain the ability to alkylate DNA and confer toxicity.