Muscle readily adapts to resistance exercise, but to date, little data is available linking the MAPK signaling pathways to these adaptations. PURPOSE: This study was designed to quantify the relative activation via phosphorylation of the ERK1/2 MAPK pathway in human skeletal muscle in subjects with varied weight training backgrounds. METHODS: Subjects were national and international caliber competitive weightlifters (WL, n=6) or powerlifters (PL, n=5), recreationally trained men with 10 wks of circuit weight training experience (CWT, n=8), or sedentary controls (CON, n=3). All subjects provided muscle biopsies from the vastus lateralis muscle. Samples were lysed and ERK1/2 and phosphorylated ERK (ERK-P) were determined via SDS-PAGE and western blots using infrared markers. Data were analyzed via one-way ANOVA and LSD post-hoc tests. RESULTS: WL & PL had less total ERK1/2 than CWT or CON (p<0.05; OD [arbitrary units]; WL=1385 ± 202, PL=1957 ± 142, CWT=4401 ± 723, CON= 3733 ± 600; X ± SE), with a moderate effect size observed for the CWT group when compared to CON (Cohen's D= 0.64). Similar patterns were observed for ERK-P (OD; WL=474 ± 34, PL=1148 ± 89, CWT=2284 ± 372, CON= 2228 ± 178). When expressed as % of total ERK1/2 phosphorylated (%ERK-P), no significant differences were observed (%; WL=39.3 ± 7.6, PL=59.3 ± 4.2, CWT=51.9 ± 3.5, CON=63.0 ± 10.9), although a large effect size was apparent for the WL when compared to CON (D=1.25). CONCLUSIONS: Chronic weight training appears to influence resting levels of ERK1/2 MAPK pathway activity. Total ERK1/2 is modestly increased in recreationally trained individuals, while elite lifters with training histories of >10 yrs exhibit attenuated total ERK 1/2. This response pattern suggests increased ERK1/2 as an initial response to resistance exercise, while long-term training experience and elite-level performances may result in either a more efficient ERK1/2 MAPK pathway, or simply reduced activation of this system. The absolute levels of ERK-P appear to simply reflect total ERK1/2 levels, with ERK-P decreasing with total ERK 1/2. In summary, elite lifters exhibit altered activation of the ERK 1/2 MAPK pathway primarily by altering total ERK1/2 available. Additionally, elite lifters appear to require less ERK activation, perhaps reflective of a more efficient signal or less stimulus for ERK activation. Funded by The University of Memphis FedEx Institute of Technology Research Investment Fund and the National Strength and Conditioning Association