Beginning in early 2006, an ocular disease of unknown etiology was routinely observed in American crocodiles (Crocodylus acutus) inhabiting the highly polluted Tarcoles River in west-central Costa Rica. We examined the nature and incidence of ocular disease in Tarcoles crocodiles and assessed the possible association between the disease and accumulation of chemical pollutants in diseased individuals. During 12–15 September and 12–13 December 2007, crocodiles were captured and examined for ocular disease and sampled to determine environmental contaminant accumulation. Three of 11 (27.3%) crocodiles captured (all males) exhibited unilateral ocular disease, primarily characterized by corneal opacity and scarring, anterior synechia, and phthisis bulbi. Multiple pollutants were detected in crocodile caudal scutes (organochlorine pesticides [OCPs] and metals), crocodile blood (OCPs), and sediments (OCPs and metals) from the Tarcoles, but no associations were found between contaminant accumulation and the incidence of eye disease. On the basis of the limited number of diseased animals examined and the potential exposure of crocodiles to pathogens and other pollutants not targeted in this study, we cannot rule out infection or chemical toxicosis as causes of the eye lesions. However, circumstantial evidence suggests that the observed ocular disease is likely the result of injury-induced trauma (and possibly secondary infection) inflicted during aggressive encounters (e.g., territorial combat) among large adult crocodiles living at relatively high densities.