Trifluoperazine showed some significant antimicrobial activity when tested against 293 strains from two Gram-positive and eight Gram-negative genera. Minimum inhibitory concentrations of the drug were measured using an agar dilution technique. Forty six of 55 strains of Staphylococcus aureus were inhibited by 10–50 μg/ml of trifluoperazine. This drug also inhibited strains of Shigella spp., Vibrio cholerae and V. parahaemolyticus at a concentration of 10–100 μg/ml. Other bacteria including Pseudomonas spp. were moderately sensitive to trifluoperazine. In the in vivo studies this compound offered significant protection to Swiss albino mice at a concentration of 30 μg/mouse ( P<0.001) when challenged with 50 median lethal dose of Salmonalla typhimurium NCTC 74.