Resistance exercise stimulates myofibrillar protein synthesis (MPS) but the influence of exercise intensity and age on MPS is poorly understood. The present aim was to investigate how MPS and activation of anabolic signalling was affected by resistance exercise at two different intensities in postabsorptive healthy men, young (n=3, 25±5 y, body mass index (BMI) 23±2 kg.m^-2) and elderly (n=4, 69±3 y, BMI 24±2 kg.m^-2). We hypothesized that phosphorylation of signaling molecules and MPS would be increased by resistance exercise in a dose dependant fashion in young and elderly men but to a lesser extent in the older men. The subjects performed isotonic unilateral leg extension at 40 and 75% of 1 repetition maximum with similar total work outputs. Muscle biopsies were taken from the vastus lateralis of the exercised leg under local anaesthesia (1% lignocaine sc) before, immediately after and 1, 2 and 4 h after exercise. After separation of myofibrillar protein, incorporation of [1,2-¹³C]leucine was used to measure MPS (by gas chromatography-combustion-mass spectrometry using plasma labeling of plasma α-ketoisocaparoate as surrogate precursor); Western analysis of sarcoplasmic protein, using anti-phosphoantibodies was used to measure the phosphorylation state of a variety of molecules involved in regulation of initiation of protein synthesis. The results (Figure 1) demonstrate that: (i) exercise at either intensity acutely reduced phosphorylation of 4EBP1, consistent with a decrease in initiation of protein synthesis, but only increased it above basal in the post exercise period in the young men; (ii) in young men, exercise at both intensities increased MPS significantly, with increases at 75% 1RM tending to be larger than those at 40%, but exercise was not associated with any significant increase above basal in elderly men. The anabolic resistance of MPS to amino acids in the elderly previously reported by us (Cuthbertson et al 2005) appears to have a counterpart in the responses of the processes of muscle protein synthesis after exercise in the absence of additional amino acids. There appears not to be a close relationship between the extent of activation of initiation of protein synthesis and the degree of stimulation of MPS after exercise.