In contrast to the effect of nutritional intervention on postexercise muscle protein synthesis, little is known about the potential to modulate protein synthesis during exercise. This study investigates the effect of protein coingestion with carbohydrate on muscle protein synthesis during resistance-type exercise. Ten healthy males were studied in the evening after they consumed a standardized diet throughout the day. Subjects participated in two experiments in which they ingested either carbohydrate or carbohydrate with protein during a 2-h resistance exercise session. Subjects received a bolus of test drink before and every 15 min during exercise, providing 0.15 g x kg(-1) x h(-1) carbohydrate with (CHO + PRO) or without (CHO) 0.15 g x kg(-1) x h(-1) protein hydrolysate. Continuous intravenous infusions with l-[ring-(13)C(6)]phenylalanine and l-[ring-(2)H(2)]tyrosine were applied, and blood and muscle biopsies were collected to assess whole body and muscle protein synthesis rates during exercise. Protein coingestion lowered whole body protein breakdown rates by 8.4 +/- 3.6% (P = 0.066), compared with the ingestion of carbohydrate only, and augmented protein oxidation and synthesis rates by 77 +/- 17 and 33 +/- 3%, respectively (P < 0.01). As a consequence, whole body net protein balance was negative in CHO, whereas a positive net balance was achieved after the CHO + PRO treatment (-4.4 +/- 0.3 vs. 16.3 +/- 0.4 micromol phenylalanine x kg(-1) x h(-1), respectively; P < 0.01). In accordance, mixed muscle protein fractional synthetic rate was 49 +/- 22% higher after protein coingestion (0.088 +/- 0.012 and 0.060 +/- 0.004%/h in CHO + PRO vs. CHO treatment, respectively; P < 0.05). We conclude that, even in a fed state, protein coingestion stimulates whole body and muscle protein synthesis rates during resistance-type exercise.