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 Acute Exposure/ The ability of ammonium chloride (NH4Cl) treatment to alter the pharmacological effects and biodisposition of phencyclidine (PCP) was investigated in rats. Either a single gavage of NH4Cl (2.5 mEq/kg) or six hourly gavages with either 2.5 or 5.0 mEq/kg of NH4Cl decreased urinary pH to approximately 5.5 at the 7-hr time point. A single gavage with NH4Cl (2.5 mEq/kg) failed to alter the time course of rotarod performance in rats that had been treated 45 min earlier with either 10, 25 or 50 mg of PCP per kg (p.o.). A treatment regimen of six hourly gavages of NH4Cl (5.0 mEq/kg) proved to be highly toxic, whereas gavages with 2.5 mEq/kg did not produce overt effects. Six hourly treatments with the lower dose of NH4Cl did not alter motor impairment induced by oral doses of 10 and 25 mg/kg of PCP but did diminish that produced by 50 mg/kg. This treatment regimen also produced a slight reduction in the time course of motor dysfunction in rats receiving an i.v. injection of either 5, 10 or 15 mg/kg of PCP. The biodisposition of orally administered (3)H PCP (50 mg/kg) was altered by six hourly gavages of 2.5 mEq/kg of NH4Cl in that urinary excretion of (3)H PCP was increased whereas concentrations in kidney, lung and brain were significantly decreased at selected times. However, the brain concentrations of (3)H PCP, as measured by area under the curve, were not altered significantly by NH4Cl treatments.