In general, mutations have a negative effect on man. Considering the great number of substances inducing mutagenic effects in microorganisms and in cell cultures, the question arises whether these substances are a genetic risk for man, too. Final statements concerning this matter should be based on in vivo investigations which fully take into account the mammalian and/or human metabolism. On the other hand, the additional costs of routine mutagenicity screening should have no inhibitory effect on the development of new drugs and other important substances. On the basis of these considerations, this paper deals with methods suitable for being incorporated into routine in vivo mutagenicity testing in mammals.