The biochemical effects and comparative nephroxicity of mercury II chloride (HgCl2) dosed at 0.75 mg/kg i.p. was investigated in the Fisher 344 rat (F344) and Mastomys natalensis using high resolution 1H nuclear magnetic resonance (NMR) spectroscopy of urine, histopathology and clinical chemical techniques. The effects of HgCl2 treatment were followed for up to 4 days post-dosing (p.d.). In F344 rats there was extensive proximal tubular damage and renal cortical necrosis together with elevated levels of urinary gamma-glutamyl transpeptidase (gamma GT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH). The 1H NMR spectra of urine obtained from Hg-treated F344 rats also showed increased levels of glucose, alanine, lactate, valine and hippurate (0-48h p.d.) with decreased levels of citrate, succinate and 2-oxoglutarate (24-48h p.d.). Mastomys were found to be highly resistant to HgCl2 toxicity at 0.75 mg/kg and the histological appearance of the renal cortex of treated animals was virtually identical to controls. There were no elevations in urinary ALP, gamma GT and LDH activities in HgCl2-treated Mastomys and there were no biochemical abnormalities in low MW components of Mastomys urine following HgCl2-treatment, as shown by 1H NMR spectroscopy. Urinary gamma GT activity was found to be much higher in F344 rats than Mastomys. Since gamma GT activity is involved in the tubular reabsorption of Hg2+, the lower levels of gamma GT in Mastomys might partially account for the lower toxicity of Hg2+ in this species.