The severity of renal injury induced by several graded doses of mercuric chloride and the disposition of mercury were evaluated and compared in control, uninephrectomized (50% NPX), and 75% nephrectomized (75% NPX) rats in an attempt to determine the effect of increased reductions of renal mass on the nephropathy induced by inorganic mercury. Consistent with previously published findings, proximal tubular necrosis (as assessed histopathologically and by the urinary excretion of lactate dehydrogenase (LDH) and total protein) was significantly more severe in 50% NPX rats than in control rats 24 hr after the administration of any of three lowest (1.0, 1.5, or 1.75 micromol/kg) doses of mercuric chloride used in the study. Interestingly, the severity of proximal tubular necrosis in the 75% NPX rats was not greater than that in control rats at these same doses. The reason for this appeared to be due to decreased renal accumulation of mercury, particularly in the renal cortex and outer stripe of the outer medulla. At the highest (8.0 micromol/kg) dose of mercuric chloride used, renal tubular injury was very extensive in all three groups of rats, with the level of injury being greatest in the 50% NPX rats. The injury was so severe in all three groups that acute renal failure was induced within the first 24 hr after the injection of mercury. An important finding that was made at this dose was that the level of blood urea nitrogen (BUN) was significantly greater in the 75% NPX rats than in either the 50% NPX or control rats, which indicates that 75% NPX rats may have entered into acute renal failure sooner than the 50% NPX or control rats. Overall, the findings from the present study indicate that as renal mass is reduced to a level at which renal function is not significantly impaired (50% NPX), the severity of the nephropathy induced by mercury is increased. By contrast, when the reduction of renal mass progresses to a level at which renal function begins to become impaired, the level of proximal tubular injury is not greatly different from that of animals with two kidneys, especially at low nephrotoxic doses of inorganic mercury. In addition, low nephrotoxic doses of inorganic mercury do not appear to affect significantly the reduced glomerular filtration rate in 75% NPX rats. However, it does appear that 75% NPX rats may be at greater risk of entering into acute renal failure at higher toxic doses of inorganic mercury than 50% NPX or control rats.