Training protocols apply sequential bouts of resistance exercise (RE) to induce the cellular and molecular responses necessary to produce compensatory hypertrophy. This study was designed to 1) define the time course of selected cellular and molecular responses to a single bout of RE and 2) examine the effects of interbout rest intervals on the summation of these responses. Rat muscles were exposed to RE via stimulation of the sciatic nerve in vivo. Stimulated and control muscles were obtained at various time points post-RE and analyzed via Western blot and RT-PCR. A single bout of RE increased intracellular signaling (i.e., phosphorylations) and expression of mRNAs for insulin-like growth factor-I system components and myogenic markers (e.g., cyclin D1, myogenin). A rest interval of 48 h between RE bouts resulted in much greater summation of myogenic responses than 24- or 8-h rest intervals. This experimental approach should be useful for studying the regulatory mechanisms that control the hypertrophy response. These methods could also be used to compare and contrast different exercise parameters (e.g., concentric vs. eccentric, etc.).