1. Urinary alkalinisation may be helpful in treating acute poisoning with uncouplers of oxidative phosphorylation containing a phenolic hydroxyl (pKa 4-6) or other acidic moiety. 2. We studied the effects of urine alkalinisation and acidification on the tissue distribution of hexachlorophene (HCP, pKa 5.7) in male Sprague Dawley rats (10 rats/group). 3. Ammonium chloride (10 mL kg-1, 2% m/v) or sodium bicarbonate (10 mL kg-1, 2% m/v) were administered by gavage on three occasions over 24 h, prior to a single gavage dose of HCP (180 mg kg-1). Controls received aqueous sodium chloride (10 mL kg-1, 0.9% m/v) followed by either HCP (180 mg kg-1) or vehicle alone. 4. Urine pH, body mass and body temperature were monitored during the study and, at the conclusion of the experiment (12 h post-HCP dose), organ mass (liver, kidney, brain), and plasma, urine and tissue HCP concentrations were measured. 5. No clinical features of toxicity were observed in any group. However, sodium bicarbonate significantly reduced median HCP in liver--median plasma and kidney HCP concentrations were also reduced but not significantly. Conversely, ammonium chloride significantly increased median HCP concentrations in liver and kidney--median plasma HCP was also increased but not significantly. 6. The results provide some support for the hypothesis that blood pH influences the tissue distribution of uncouplers of oxidative phosphorylation containing an acidic moiety. Urinary alkalinisation may be useful in treating acute poisoning with these compounds.