Previous studies from this laboratory have indicated that dithiothreitol (DTT) administration (31 mg DTT/kg, i.p.) 1 h after mercuric chloride injection (3 mg/kg, i.v.) results in partial reversal of Hg-induced renal toxicity without altering total renal mercury deposition. Studies were performed, therefore, to determine if DTT administration altered the renal delivery, excretion, and/or, in particular, subcellular distribution of mercury in a way that may explain the observed phenomenon. Analysis of mercury partitioning between red cells and plasma revealed no difference in relative distribution when Hg- or Hg + DTT-treated groups were compared. However, absolute mercury concentration in both whole blood and plasma of Hg + DTT-treated rats was significantly higher than in the Hg-treated group. Total urinary excretion of mercury was significantly less in Hg + DTT-treated rats than in rats treated with mercury alone. The subcellular distribution of mercury in the particulate and supernatant fractions of renal cortical homogenates from Hg-treated and Hg + DTT-treated rats was similar. Fractionation of the supernatant on G-75 Sephadex gel revealed no difference in the protein profiles between the Hg- and Hg + DTT-treated groups. It is concluded that DTT administration ameliorates the nephrotoxic effect of prior mercury injection by a more subtle mechanism than redistribution of renal cortical mercury.