Mercury (Hg) impairs glutamate homeostasis but little is known about its effects on the N-methyl-d-aspartic acid (NMDA) receptor. Here, we investigated NMDA receptor levels, as determined by [(3)H]-MK801 binding, in both wild and captive mink (Mustela vison) that experienced different levels of methylmercury (MeHg) exposure. Competitive in vitro binding experiments showed that inorganic Hg (HgCl(2); IC(50)=1.5-20.7 microM), but not MeHg (MeHgCl; IC(50)>320 microM), inhibited binding to the NMDA receptor in several brain regions of mink. In a survey of trapped wild mink, NMDA receptor levels in the brain were negatively correlated (p<0.005) with concentrations of total Hg (R=-0.618) and MeHg (R=-0.714). These findings were supported by a laboratory feeding study in which captive mink were exposed to dietary MeHg (0-2 ppm) for 89 days. Concentration-dependent decreases in NMDA receptor levels were found in the basal ganglia, cerebellum, brain stem and occipital cortex. These findings are of physiological and ecological concern because they demonstrate that Hg, at dietary concentrations as low as 0.1 ppm, can significantly reduce NMDA receptor levels.