Much of our knowledge on the physiological mechanisms of transcranial magnetic stimulation (TMS) stems from studies which targeted the human motor cortex. However, it is still unclear which part of the motor cortex is predominantly affected by TMS. Considering that the motor cortex consists of functionally and histologically distinct subareas, this also renders the hypotheses on the physiological TMS effects uncertain. We use the finite element method (FEM) and magnetic resonance image-based individual head models to get realistic estimates of the electric field induced by TMS. The field changes in different subparts of the motor cortex are compared with electrophysiological threshold changes of 2 hand muscles when systematically varying the coil orientation in measurements. We demonstrate that TMS stimulates the region around the gyral crown and that the maximal electric field strength in this region is significantly related to the electrophysiological response. Our study is one of the most extensive comparisons between FEM-based field calculations and physiological TMS effects so far, being based on data for 2 hand muscles in 9 subjects. The results help to improve our understanding of the basic mechanisms of TMS. They also pave the way for a systematic exploration of realistic field estimates for dosage control in TMS.