The growth inhibition of Escherichia coli and Staphylococcus aureus was accompanied by significant release of K+ and UV-absorbing small molecules upon exposure to methdilazine, an extensively used phenothiazine antihistamine. A severe decrease in [U-14C] glucose uptake and a rapid efflux of hexose from sugar-preloaded bacteria were also observed but without visible cellular lysis. Considerable damage to membrane permeability by methdilazine was proposed to explain the rapid loss in cfu/mL of the bacteria.