To assess the effect of agriculture drain water, a complex mixture containing pesticides and selenium (Se), on the physiological stress response, white suckers were collected from irrigation return flows in the summer and the fall and subjected to a stress challenge. Water (0.40-26.71microg/L) and muscle Se (0.37-1.52microg/g ww) levels were elevated at two sites and plasma acetylcholinesterase (AChE) activity (a marker of pesticide exposure) was lower in the fall (5.97+/-0.45micromol/min/mL) than the summer (10.73+/-0.73micromol/min/mL). Fish raised plasma cortisol levels in response to the stress challenge 11.8 times above basal levels (12.8+/-4.9ng/mL). Multivariate statistics linked Se exposure to elevated plasma glucose levels, and pesticide exposure to elevated liver glycogen levels generating hypotheses for further testing. This study showed that white suckers accumulated Se from agricultural drain water and the complex mixtures present in the drain water influenced the physiological stress response.