The effect of isotonic mannitol and saline in the early phase of mercuric chloride- (HgCl2-)induced acute renal failure (ARF) in the dog was evaluated. During the first 3 h after HgCl2 alone, glomerular filtration rate (GFR) fell from 1.94 ± 0.14 to 1.04 ± 0.11 and renal blood flow (RBF) from 13.99 ± 1.18 to 7.28 ± 0.77 ml/min·kg BW. Isotonic mannitol alone resulted in a fall of GFR by 22% (p < 0.05 vs. control), but the subsequent administration of HgCl2 could not induce a further fall in GFR and RBF. A similar, if somewhat less pronounced, protective effect was observed when mannitol was started simultaneously with or 2 h after the HgCl2 injection. Infusion of isotonic saline at the same rate as mannitol did not prevent a fall of GFR and RBF from a premercury value of 2.33 ± 0.31 to 1.36 ± 0.26 and 16.83 ± 3.06 to 9.30 ± 2.65 ml/min·kg BW, respectively. In contrast, massive doses of isotonic saline, provoking urinary volume and solute losses comparable to those observed with mannitol, stabilized GFR after HgCl2 at the normal level (ΔGFR = -3%). No relationship between ΔGFR and urinary Hg excretion or renal tissue Hg content could be established. In summary, isotonic mannitol prevented the fall of GFR normally observed in the early phase of HgCl2-induced ARF. This effect was not volume mediated and not due to a higher Hg excretion. The protection was correlated with its osmotic diur