The influence on the mutagenicity of cyclophosphamide (Cy) and epichlorohydrin (ECH), of liver nuclei and hepatic post-mitochondrial (S9) preparations from phenobarbital-treated rats, was examined. The study was conducted in vitro, with 2 yeasts, Schizosaccharomyces pombe (P1 strain) which allows the detection of forward mutations, and Saccharomyces cerevisiae (D5 strain), in which the induction of different genetic effects, such as mitotic recombination, can be evaluated. The results indicated that the nuclear fraction has a qualitative capacity for biotransformation of compounds, overlapping that of S9. From a quantitative point of view, the Cy-activating capacity of the nuclear fraction was twice as high as that of S9 whereas the two fractions showed a similar ECH-inactivating ability. The present study strengthens the hypothesis of the relevance of nuclei as a site of metabolic activation and inactivation of exogenous compounds.