Land-treatment of petroleum wastes is a widely used industrial practice, yet there has been no comprehensive evaluation of the long-term risks to human or terrestrial ecosystems from such practices. We evaluated cotton rat (Sigmodon hispidus) populations on three sites in Oklahoma (USA) that historically used land-treatment for disposal of various petroleum wastes (July 1995–March 1997). Average concentrations of fluoride in soil from these sites ranged from 878 to 4317 mg/kg. A census of resident cotton rats on land-treatment sites revealed a high incidence (40% overall) of dental lesions compared to reference populations (<1% dental lesions). During winter there was a 34% to 65% increase compared to summer in frequency of dental lesions in cotton rats on two of the three land-treatment sites. Incidence of dental lesions on two land-treatment sites was greater (9–16%) in female cotton rats compared to males. Cotton rats from land-treatment sites had higher concentrations of fluoride in bone and greater severity of dental lesions compared to reference animals. Dental lesions were considered to be most consistent with dental fluorosis because of elevated fluoride in bone. Neither concentration of fluoride in soil nor level of fluoride in bone was a good predictor of severity of dental lesions in cotton rats on land-treatment sites.