Methyl tertiary-butyl ether (MTBE) is a gasoline oxygenate blended into fuel formulas in the 1990s to decrease carbon monoxide emissions. Although MTBE was banned from use as a fuel additive in 2006, it has been detected in public drinking water in several states throughout the country and elsewhere in the world. Now the EPA must regulate MTBE contamination in ground and surface waters. Although the health risk of human exposure to low doses of MTBE is unknown, long-term rodent cancer bioassays using high concentrations of MTBE increases the incidence of tumors at various organ sites. The two studies presented in this thesis are the latest in a series of experiments at this university designed to better understand how MTBE causes an increase in endocrine-related tumors. The research from the first experiment reported here focuses on the incorporation of more standardized measures of generalized toxicity (e.g., stress response) that are very important for understanding the MTBE-related endocrinological changes in relation to the broader toxicological perspective. Previous studies also demonstrate MTBE-induced renal damage in the proximal tubules of male rats through interaction with [lower case alpha]-2u-globulin. A second study explores the use of novel urinary proteins as biomarkers of renal damage induced by MTBE exposure. In the first experiment (n=16) Sprague-Dawley male rats were gavaged with 0 (corn oil), 600 or 1200 mg/kg MTBE per day for 14 consecutive days. In the second experiment (n=5) Sprague-Dawley male rats were gavaged with 0 (corn oil) or 1200 mg/kg MTBE per day for 14 consecutive days. Serum corticosterone concentrations were measured in the first study and showed a significant increase (p<0.05) in the 1200 mg/kg MTBE treated group. Hepatorenal serum chemistry was measured in both studies and revealed no differences between treated and control animals. However, in the second study two of the six urinary protein concentrations ([lower case beta]-2-microglobulin and cystatin C) displayed significant increases (p<0.05) in the 1200 mg/kg MTBE treated group relative to the control group. Therefore, urinary protein concentrations proved to be more sensitive biomarkers of renal changes than conventional serum chemistry (BUN and creatinine) following subchronic high dose oral MTBE exposure. Although MTBE induced endocrine change has been the focus of previous experiments, the two current studies reveal other exposure related systemic changes that could also affect alteration in endocrine function.