Lactate removal by inactive skeletal muscle was investigated using an isolated rat hindlimb perfusion model under conditions simulating recovery from maximal exercise. The purpose of this investigation was threefold: 1) to quantify the contributions of the oxidative, glyconeogenic, and triacylgylcerol (TG) synthesis pathways to lactate (La) removal, 2) to examine differences in La removal patterns in inactive skeletal muscle of various fiber types, and 3) to investigate the possible mechanisms for La and H⁺ removal by inactive muscle. Male Sprague-Dawley rats were perfused for 60 min, at rest with either a normal perfusate (NP) (N = 8) or a lactacidotic perfusate (LP) (N = 8). The LP perfusate was characterized by elevated concentrations of La (11.0 mMol), K⁺ (7.88 mMol), and hemoglobin (16.7 g·dl⁻¹) and a decreased pH (7.15). Arterial and venous perfusate and soleus (SOL), plantaris (PLT), and white gastrocnemius (WG) muscles were analyzed for various metabolite and ion concentrations. Analysis revealed increased rates of La uptake, glycerol release and C0₂ output in the LP versus the NP group. No difference was observed for O₂ uptake or glucose uptake between the two groups. Tissue anajysis revealed no significant change in muscle ATP, CP, glycogen, pyruvate, F-6-P or TG concentration pre versus post perfusion in both LP and NP groups. Significant increases were found in muscle La concentration (pre vs post and LP vs NP), with SOL having the highest concentration followed by PLT and WG. Muscle [F-1 ,6-diP], F-1 ,6-diP /F-6-P and pyruvate/F-1 ,6-diP ratios were elevated following LP perfusion indicating glyconeogenic inhibition. Muscle glucose levels decreased in the NP but not LP group, indicating a possible shift in substrate utilization in the LP group. In the LP group, total calculated La uptake by the 3 muscles was 61.0 umole, with 14% accumulating as tissue La post perfusion. Of the remaining 86%, 12-33% could be accounted for by oxidative metabolism, and 5-7% may have been involved in glycerol release. The remaining 60-75% was unaccounted for, but was hypothesized to have been involved in carbon cycling along the glycolytic/glyconeogenic pathway and/or in TG/FFA substrate cycling. No evidence was found of net glycogen synthesis from La. Increased H⁺ and K⁺ influx and HCO₃⁻ efflux were observed in response to lactacidotic perfusion. Sodium and Cl⁻ exchange patterns showed a net influx over 60 min of LP perfusion. Data from the ionic flux of the various strong ions and non-volatile H⁺ suggested that La is transported into inactive skeletal muscle by various mechanisms, including HLa diffusion, La/H⁺ cotransport, and possibly La/Cl⁻ exchange. The data also suggested that a number of regulatory mechanisms are activated in rat skeletal muscle to maintain intracellular [H⁺] and membrane potential during lactacidotic perfusion. From this investigation it was concluded that, in inactive muscle of the isolated rat hindlimb perfused for 60 min with a lactacidotic perfusate, patterns of La uptake and metabolic elimination are different from those previously observed for active muscle. The metabolic fates of La appear to be related to the ionic disturbances associated with La and H⁺ influx into inactive muscle. The net ionic movements across the inactive hindlimb appear to be related to the preferred metabolic pathways of La elimination, but whether or not a direct cause and effect relationship exists cannot be stated conclusively. / Thesis / Master of Science (MSc)