In the present study, we tested the hypothesis that co-administration of low nephrotoxic doses of inorganic mercury (Hg++) with L-cysteine (in a 1:2 mol ratio of inorganic mercury to L-cysteine), alters significantly the nephropathy induced by inorganic mercury. In the first experiment, the effect of co-administering L-cysteine on the nephropathy induced by a 1.8 or 2.0 micromol/kg dose of inorganic mercury was evaluated in rats 24 h after the administration of inorganic mercury. According to histopathological assessment of sections of kidney and evaluation of the urinary excretion of lactate dehydrogenase, total protein and inorganic mercury (which were used as indices of renal injury), the severity of renal injury in rats co-administered the L-cysteine with the inorganic mercury was significantly greater than that in corresponding rats injected with only inorganic mercury. In a second experiment, the disposition of mercury was evaluated 1 h after the administration of 1.8 micromol inorganic mercury/kg with or without 3.6 micromol L-cysteine/kg. The renal accumulation of mercury, specifically in the cortex and outer stripe of the outer medulla, was significantly greater the rats co-administered the inorganic mercury and L-cysteine than in the rats given only inorganic mercury. In addition, the content of mercury in the blood and liver was significantly lower, and the fraction of mercury in the blood present in the plasma was significantly greater, in the rats co-administered inorganic mercury and L-cysteine than in the rats given only inorganic mercury. On the basis of the findings from this study, the nephropathy induced by low nephrotoxic doses of inorganic mercury is made more severe when the inorganic mercury is co-administered in a 1:2 mol ratio with L-cysteine. Moreover, it appears that the enhanced severity in the nephropathy induced by the co-administration of inorganic mercury and L-cysteine is linked to an increase in the tubular uptake of mercury in the cortex and outer stripe of the outer medulla.