The neuregulin/erbB-signaling axis contributes to the development and growth of multiple mammalian tissues including skeletal muscle. In this study, we sought to characterize the native expression of this system in human skeletal muscle and test the hypothesis that a program of progressive resistance training (PRT) would regulate the expression of neuregulin (NRG) and its cognate receptors. Twelve healthy-male subjects underwent 8-weeks of lower-extremity PRT and muscle biopsies were performed at baseline and following 1- and 8-weeks of the intervention. PRT resulted in significant gains in skeletal muscle strength without appreciable changes in fiber size or myosin heavy chain (MHC) composition. At baseline, Western Blot analysis demonstrated expression of erbB2, erbB3 and erbB4 receptors and multiple NRG isoforms. Following 1- and 8-weeks of PRT, no changes erbB2, erbB4 or NRG expression were observed. ErbB3 expression, however, was significantly increased at both time points compared to baseline. Double labeling of muscle cross-sections revealed increased expression of erbB3 following PRT was not exclusive to fibers staining positive for MHC IIa. Thus, erbB2, erbB3, erbB4 and multiple NRG isoforms are natively expressed in human skeletal muscle. Following PRT, a significant increase in erbB3 was observed. The ability to detect basal expression and alterations in response to physiologic stimuli merit further studies examining the role of this system in skeletal muscle.