Despite their ecological importance and global decline, snakes remain poorly studied in ecotoxicology. In this study, we examined organochlorine (OC) pesticide and mercury accumulation in cottonmouths (Agkistrodon piscivorus) living on a contaminated site in northeastern Texas (USA). Mercury and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) were detected in all snakes examined. Other OCs, including p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), methoxychlor, aldrin, and heptachlor, also were detected, but less frequently. Concentrations of p,p'-DDE were higher in fat than in liver, while mercury concentrations were highest in liver, followed by kidney and tail clips. One animal contained the highest mercury concentration yet reported for a snake (8,610 ng/g). Mercury concentrations in liver and kidney were higher in males than females, while no intersex differences in p,p'-DDE concentrations were observed. Concentrations of p,p'-DDE in fat were correlated positively with body size in male cottonmouths but not females, suggesting a slower rate of accumulation in females. Body size strongly predicted mercury concentrations in liver, kidney, and tail clips of both sexes. Tail clips were strong predictors of mercury in liver and kidney in males but not females, suggesting possible sex-dependent differences in mercury toxicokinetics. Both long-term field studies and controlled laboratory investigations are needed to adequately assess the response of cottonmouths to chronic contaminant exposure.