The metabolic transformation of chlorinated aliphatic hydrocarbons to reactive intermediates is predominantly determined by the number of chlorine substitutions and the type of C-C bonds. Due to their electron-attracting effect, chlorine residues exert a destabilization in alkanes, resulting in metabolic conversions to either alkenes (dechlorination or dehydrochlorination) or free radicals. Chlorinated alkenes are enzymatically oxidized to epoxides which may be hydrolized (enzymatically or nonenzymatically), react with cellular nucleophiles, or rearrange to either chlorinated aldehydes or acyl chlorides. In the series of chlorinated ethylenes (tetra-, tri-, 1,2-cis- and trans-di-, 1,1-di-, and monochloroethylene) the metabolites thus far identified are identical to or biological conjugates of the expected thermal rearrangement products of the epoxides, with one important exception: trichloroethylene. The thermal rearrangement of this epoxide leads to dichloroacetylchloride; in vivo, however, only chloral hydrate (or further derivatives of it) is found. It is suggested that a Lewis acid-like catalysis is responsible, at the site of epoxide formation, for this striking difference in the behavior in vitro and in vivo. Mutagenic and possible carcinogenic activities of the chlorinated ethylenes may be a function of the stability of the epoxides, which is higher in symmetric than unsymmetric substituted molecules. Little is known about the metabolic fate of chlorinated alkynes where the chlorine substitution in general results in a destabilization of the molecules. The neurotoxic activity of dichloroacetylene is discussed