The aim of the present study was to examine the effect of beta2-adrenergic stimulation on skeletal muscle contractile properties, sarcoplasmic reticulum (SR) rates of Ca(2+) release and uptake, and Na(+)/K(+)-ATPase-activity before and after fatiguing exercise in trained men. The study consisted of two experiments (EXP1, n = 10 M, EXP2, n = 20 M), where beta2-adrenoceptor agonist (terbutaline) or placebo was randomly administered in double-blinded crossover designs. In EXP1, maximal voluntary isometric contraction of m.quadriceps (MVC) was measured, followed by exercise to fatigue at 120% of Vo2max. A muscle biopsy was taken after MVC (non-fatigue) and at time of fatigue. In EXP2, contractile properties of m.quadriceps were measured with electrical stimulations before (non-fatigue) and after two fatiguing 45-s sprints. Non-fatigued MVC was 6±3 and 6±2% higher (P < 0.05) for terbutaline than placebo in EXP1 and EXP2. Furthermore, peak twitch force was 11±7% higher (P < 0.01) for terbutaline than placebo at non-fatigue. After sprints, MVC declined (P < 0.05) to same levels for terbutaline as placebo, whereas peak twitch force was lower (P < 0.05) and half relaxation time prolonged (P < 0.05) with terbutaline. Rates of SR Ca(2+) release and uptake at 400 nM [Ca(2+)] were 15±5 and 14±5% (P < 0.05) higher for terbutaline than placebo at non-fatigue, but declined (P < 0.05) to similar levels at time of fatigue. Na(+)/K(+)-ATPase-activity was unaffected by terbutaline compared with placebo at non-fatigue, but terbutaline counteracted exercise-induced reductions in Vmax at time of fatigue. In conclusion, increased contractile force induced by beta2-adrenergic stimulation is associated with enhanced rate of Ca(2+) release in humans. While beta2-adrenergic stimulation elicits positive inotropic and lusitropic effects of non-fatigued m.quadriceps, these effects are blunted when muscles fatigue. This article is protected by copyright. All rights reserved.