This study tested the hypothesis that increasing the protein content of isocaloric meals increases the rate of myofibrillar synthesis in muscle of healthy subjects over 60 yr old and enhances the stimulation of myofibrillar synthesis induced by resistance exercise. Myofibrillar synthesis of sedentary and exercised quadriceps muscle was determined by incorporation of L-[1-13C]leucine. During the tracer infusion, subjects consumed meals with a low (7% of energy, n = 6)-, normal (14%, n = 6)-, or high (28%, n = 6)-protein content. In sedentary muscle, the mean (+/- SE) myofibrillar synthesis was 1.56 +/- 0.13%/day in the low-protein group, 1.73 +/- 0.11 %/day in the normal-protein group, and 1.76 +/- 0.10%/day in the high-protein group (P = 0.42). Myofibrillar synthesis was faster in exercised muscle (mean 27%, P < 10(-6) in all groups (2.10 +/- 0.14%/day in low protein; 2.18 +/- 0.10%/day in normal protein; 2.11 +/- 0.09%/day in high protein; P = 0.84). The stimulation of myofibrillar synthesis by exercise was not significantly different among low-protein [0.54 +/- 0.12%/day (37 +/- 9%)], normal-protein [0.46 +/- 0.08%/day (28 +/- 5%)], and high-protein groups [0.34 +/- 0.04%/day (20 +/- 3%); P = 0.31]. We conclude that high-protein meals do not enhance the stimulation of myofibrillar protein synthesis induced by resistance exercise.