Dermatomyositis (DM) is an idiopathic inflammatory disorder consisting of skin and skeletal muscle involvement. Some drugs induce DM or dermatomyositis-like syndrome (DM-LS), the others provoke polymoysitis (PM) or cause elevation of serum levels of muscle enzymes (SE) or give muscle damage (M). The unexpected adverse reactions to drugs causing myositis are not a solved contemporary problem. The aim of this study was to determine the structural requirements of eliciting drug-induced DM as compared with drug induced PM. The Common Reactivity Pattern (COREPA) approach was used to describe the structural requirements for eliciting side effects of 20 drugs, such as DM and combined activities as DM+DM-LS and PM+M+SE. The specific atoms (atomic groups) defined to have characteristic ranges for their electronic properties (atomic charges) were found to be indicative for the possible active centers responsible for eliciting the adverse effects. Reduced sulphur in the charge range of -0.07 < Qs < -0.450 a.u. and a nitrogen atom (in a cyclical fragment or anticyclical in a sp3-hybridization) in a charge range of -0.390 < QN < -0.140 a.u. were found as active centers for DM and DM+DM-LS side effects. In other group of drugs, the oxygen atoms of carbonyl and hydroxyl groups in the charge range of -0.350 < Qo < -0.320 a.u. were found to induce PM+M+SE side effects. It was found that DM requires moderate electrophilicity as compared with other chemical in the training set, whereas DM+DM-LS effect needs higher electrophilicity in the range of -0.220 < ELUMO < 0.250 eV for lowest unoccupied molecular orbital ELUMO. Similarly, PM+M+SE effect required higher electrophilicity, however, defined differently--in terms of lower values of nucleophilicity parameter EHOMO, i.e., highest occupied molecular orbital.