The purpose of this study is to 1) compare glycolytic muscle metabolism in patients with chronic fatigue syndrome (CFS) with normal humans, 2) test the feasibility of using near-infrared spectroscopy (NIRS) measurements to evaluate patients with chronic fatigue syndrome, and 3) to determine if exercise training improves muscle metabolism in CFS patients. To address these aims we tested 27 subjects controls and patients with CFS as identified by Dr. Natelson's research group. The medial gastrocnemius was studied and repeated plantar flexions were performed using a isokinetic device. CFS subjects had oxidative capacity (Vmax determined from PCr recovery) compared to control subjects, consistent with our previous studies. Seven of the 21 CFS patients had abnormal rates of H+ production during the 64 s maximal test. Three had slower H+ rates and four had faster H+ rates. NIRS measurements of the rate of oxygen resaturation showed close agreement with PCr recovery rates in control subjects (32.5 + 11 for NIRS compared to 29.9 + 4.8 s for PCr). However, NIRS recovery after exercise was slower the CFS patients than PCr recovery (48.2 + 21 for NIRS compared to 35.4 + 14 s for PCr). In addition, NIRS recovery of oxygen saturation was slower after cuff ischemia in CFS patients compared to controls (20.8 + 13 for CFS compared to 11.3 + 2.8 s for controls). Four CFS subjects have completed the training and testing protocol. Future studies will continue to test CFS patients and control subjects to complete our aims. We plan to continue testing of CFS patients and normal subjects who are enrolling in the exercise program. We also plan to follow up the NIRS findings of reduced oxygen delivery by measuring muscle blood flow in CFS patients with alternative means (Duplex Doppler flow measurements). In one CFS patient with slow NIRS recovery, Doppler measures showed normal peak blood flows, but reduced sensitivity to submaximal hyperemic stimuli.