Purpose: To study the effect of carbohydrate compared to placebo ingestion on plasma cytokines and muscle cytokine mRNA following 2.5 h of intensive cycling in 15 trained cyclists. Methods: Fifteen trained cyclists cycled for 2.5 h at 60% W-max on two occasions while receiving 4 mL(.)kg(-1.)15 min(-1) carbohydrate (6%) (CHO) or placebo (PLA) beverages in a randomized, counterbalanced design. Blood and vastus lateralis muscle biopsy samples were collected before and after exercise and 12 h postexercise and compared to samples taken from five cyclists who rested in the lab during the exercise sessions. Blood cell counts were determined, and plasma was analyzed for interleukin (IL)-6, IL-10, IL-1 receptor antagonist (ra), IL-8, cortisol, epinephrine, glucose, and insulin. Muscle was analyzed for glycogen content and relative gene expression of four cytokines, IL-6, IL-8, tumor necrosis factor (TNF) alpha, and IL-10, using real-time quantitative reverse transcriptase polymerase chain reaction. Results: Plasma glucose and insulin were higher, and epinephrine, cortisol, IL-6, IL-10, and IL-Ira, but not IL-8, were significantly lower postexercise in CHO versus PLA. Muscle glycogen content decreased 68% immediately postexercise and the pattern of change did not differ between CHO and PLA. Muscle IL-6, IL-9, TNF-alpha, but not IL-1 beta mRNA increased immediately postexercise compared to controls, with no differences between CHO and PLA. Conclusion: CHO compared to PLA beverage ingestion attenuated the increase in plasma cortisol, epinephrine, IL-6, IL-10, and IL-Ira, but not muscle IL-6, IL-8, and TNF-alpha mRNA in athletes cycling 2.5 h at 60% W-max.