Previous research on overtraining due to excessive use of maximal resistance exercise loads (100% 1 repetition maximum; 1RM) indicates that peripheral muscle maladaptation contributes to overtraining-induced performance decrements. Purpose: This study examined the cellular and molecular responses of skeletal muscle to performance decrements due to high relative intensity (% 1 RM) resistance exercise overtraining. Methods: Weight-trained men were divided into overtrained (OT, n=8) and control (CON, n=8) groups. The OT group performed 10 x 1 at 100% 1 RM daily for 2 weeks, while the CON group performed normal training 2 d^.wk^-1. Muscle biopsies from the vastus lateralis m., voluntary static and dynamic muscle performances, and nocturnal urinary epinephrine were assessed pre- and post OT. Results: Overtraining occurred as indicated by a decrease in 1 RM strength for the OT group (X±SE; kg; OT pre=159.3±10.1, OT post=151.4±9.9, CON pre=146.0±12.9, CON post=144.9±13.3), as well as a 36.3% decrease in mean power at 100% 1 RM loads. Muscle 2 adrenergic receptor (2-AR; fmol.mg protein^-1) density significantly decreased by 37.0% for the OT group and was unchanged for the CON group (-1.8%). The ratio of nocturnal urinary epinephrine/2-AR density suggested a decreased 2-AR sensitivity for the OT group (2.4-fold increase). Conclusions: Overtraining occurred based on decreased muscular force and power. Desensitization of the 2-AR system suggests that this is an important contributor to performance decrements due to excessive use of maximal resistance exercise loads.