Nitrosamines, in general, require metabolic transformation to produce electrophilic metabolites. These interact with cellular nucleophiles to initiate the chain of events culminating in tumour initiation. The enzymatic hydroxylation of the alpha-carbon of nitrosamines has long been held to be an important process in the formation of carcinogenic metabolites. The present work suggests, however, that there may be other processes which also result in the formation of electrophilic species. These include: (1) beta-hydroxylation, followed by appropriate conjugation, which results in the formation of electrophilic oxadiazolium ions. (2) O-alkylation of nitrosamines, which has the effect of labilizing the alkyl groups attached to the nitrogen toward nucleophilic substitution. (3) The formation of alpha, beta-unsaturated nitrosamine (N-nitrosoenamines), which are highly reactive species that can be readily transformed to alpha-hydroxylated nitrosamines by acid-catalyzed hydration. N-nitrosoenamines also react directly with a variety of nucleophilic reagents. The isomerization of beta, gamma-unsaturated nitrosamines to the alpha, beta-unsaturated isomers has been demonstrated to occur in vivo.