The pharmacokinetic characteristics of chloroethylnitrosourea anti-cancer agents are based on their high chemical reactivity and subsequent rapid breakdown in the plasma; and on a widespread tissue distribution due to the molecules' lipophilic properties. These physico-chemical properties explain the main problems that one may face during pharmacokinetic studies (assay method, isolation of high reactive intermediates) and that are related to the typical pharmacokinetic profile of these agents: rapid gastro-intestinal absorption, short half-life, widespread pulmonary and renal distribution, passage through the blood-brain barrier with levels within a therapeutic range, lipoprotein fixation, mainly hepatic and pulmonary metabolism, renal excretion. A drug interaction with phenobarbital has been described in the rat. The rational use of these compounds in cancer chemotherapy requires the optimisation of assay methods and a better understanding of their transformation pathways as well as their mechanism of action.