The mutagenicity in Salmonella and in vivo sister chromatid exchange in the bone-marrow cells of mice was determined for 1,4-, 1,3-, 2,4-, and 3,4-dimethylphenanthrene (DMPh) with the objective to study the relative importance of substitution at the 1 and 4 positions of this series of methylated phenanthrenes. For both tests, 1,4- DMPh was decidedly more genotoxic than the remaining regioisomers. While the well recognized role of steric crowding in the bay region is a factor in this enhanced genotoxicity, equally important is substitution at the 1 position with its potential to inhibit detoxication through 9,10-diol formation.