The localization of some genes determining the capacity for some cytochrome P-450 -dependent reactions have been studied in adult Drosophila. Strains with genetically determined high or low enzyme activities were crossed with strains carrying recessive visible markers on the chromosomes, and enzyme activities were measured in microsomes from recombinant F2 progeny. A dominantly inherited high p-nitroanisole (PNA) demethylation and biphenyl 3-hydroxylation in insecticide-resistant strains were both shown to be located around 65 cM on the second chromosome, regulated by one gene or closely linked genes. This localizes these activities to the same region as the gene responsible for the cross resistance to several classes of insecticides and a high metabolism of vinyl chloride in resistant strains. The occurrence of a regulatory gene mutation as a basis for the insecticide resistance is proposed. Hydroxylation of benzo[a]pyrene (BP) and deethylation of 7-ethoxy-coumarin seems to be determined by two third chromosome genes, at approx. 51 and 58 cM, respectively. The capacity for biphenyl 4-hydroxylation was shown to be determined by two genes on the second chromosome, one at or to the left of the gene black (48 cM) responsible for a low metabolism in strain Berlin K, and one at about 63 cM giving high formation of this metabolite in Oregon R. The latter could not be separated from the gene in insecticide-resistant strains at c:a 65 cM discussed above on the basis of the genetic localization, but observations supporting the occurrence of two closely linked genes regulating these different activities are available. In conclusion, 4-5 genes determining the capacity for several reactions, being a part of the genetic regulation of the cytochrome P-450 system in Drosophila melanogaster were indicated.