Background. Intense exercise is associated with a high production of lactate (LA) with a concomitant elevation in acidity, whereby the pH may fall ∼0.5 pH units within the exercising muscles. Exercise in a hot environment is associated with an accelerated onset of fatigue due to heat storage and the accompanying systemic and metabolic changes that occur compared to exercise in a neutral environment. While there are many factors that could lead to early muscle fatigue during exercise in the heat, research has yet to completely elucidate the interaction between metabolic and thermoregulatory factors. Purpose. The primary purpose of this study was to compare the effects of high intensity, time-to-exhaustion (TTE) cycling exercise (80- and 100% VO₂max) in hot (38°C) and cold (10°C) environments on pH, LA, bicarbonate (HCO₃^-), K⁺, and core temperature (Tc). The secondary purpose of this study was to determine the relationship between the pH threshold (pHT), lactate threshold (LT), and bicarbonate threshold (BCT). Methods. Prior to data collection, VO₂max tests were performed to assess levels of aerobic fitness (VO₂max > 3.5 L/min.), and to determine experimental workloads. A learning trial was performed in the hot environment at 80% VO₂max prior to the experimental trials. Subjects completed four separate TTE cycling trials: (1) Hot (35°C) 80% VO₂max (H80), (2) Cold (10°C) 80% (C80), (3) Hot 100% (H100), and (4) Cold 100% (C100) in a randomized, counterbalanced order. Trials were separated by a minimum of 3 days. Subjects were fitted with an esophageal probe prior to exercise in order to assess Tc. A catheter was placed in a forearm vein for blood sampling. A 5-min warm-up was completed at room temperature prior to beginning the exercise trial. Blood samples were taken at baseline, every 5-min during exercise, post-exercise, and 3-min post-exercise. A blood gas analyzer was used to measure whole blood pH, HCO₃^-, and K⁺ (Radiometer, ABL77). Lactate (LA) was measured using a spectrophotometric, enzymatic assay. VO₂ (open circuit spirometry with automated gas analysis) and heart rate (telemetry---Polar Heart Watch) data were obtained during the trials. Repeated measures 2x2x3 and 2x2x5 ANOVAs (Condition x Intensity x Time) were used to determine differences between experimental trials and Newman-Keuls post hoc analyses were used to determine where the differences occurred between the trials. Alpha was set at P < 0.05. Backwards, step-wise multiple regression was used to predict TTE using multiple dependent variables as predictors. Results. Time-to-exhaustion (TTE) was significantly different between all trials except H100 and C100. In addition, pH was significantly different at REC for all trials except H100 and C100 while LA was significantly different between trials at REC. Bicarbonate was lowest at EXH in H80 and C80, but there was no difference between these two trials; however, HCO₃ ^- was significantly lower for H80 and H100 at REC. Potassium was significantly higher at EXH when performing exercise in a hot environment. Finally, Tc was higher at EXH for H80 and C80 compared to H100 and C100. Conclusions. Core temperature likely played a greater role in muscular fatigue during the longer, less intense trials (H80 and C80), while pH and HCO ₃^- may have been more important factors during the shorter, more intense trials (H100 and C100).