The nature of the resistance mechanisms in a strain of, Musca domestica L., resistant to naphthalene was investigated after isolating the factors by genetic methods. This study was done by (Tossing the naphthalene-resistant strain with a susceptible strain caning morphological markers for chromosomes II, III, and V and backcrossing the resulting hybrids with the susceptible parent. The progeny were separated according to phenotype, and their resistance characteristics were studied in vitro and in vivo by measuring mortality response to discriminating doses of naphthalene vapors, knock-down rate after treatment wth naphthalene, tributyltin chloride, and dieldrin, and activity of microsomal enzymes. The results indicated that 3 factors are involved in resistance to naphthalene. A factor on chromosome II is related to microsomal cnzymes and endows the strain carrying it with as much as 10 times the normal oxidase activity. The 2nd resistance factor, situated on chromosome III, results in a reduced rate of penetration of the cuticle, knockdown rates of strains carrying this factor being about ½ those of other strains. A factor on chromosome V, less important than the others, could not be so completely characterized, However, its effect in combination with the 2nd and 3rd chromosomal factors was significant. Each of the factors alone, in the respective backcross phenotypes, provided about 2-fold resistance to naphthalene vapors but when combined in the resistant parent gave a protection of 6- to 10-fold, depending upon the age of the insects.