Of nine antihistamines screened for in vitro antibacterial activity, ambodryl (bromodiphenhydramine hydrochloride) and benadryl (diphenhydramine hydrochloride) were the most active. At 50 to 100 μ/ml concentrations these inhibited a large number of Gram negative and Gram positive bacteria in vitro, with ambodryl having a broader spectrum. In vivo tests showed that the compounds at single doses of 3 and 1.5 μg/g body weight protected mice against a challenge with a virulent strain (LD50) of Salmonella typhimurium, and also significantly reduced the multiplication of this organism in the liver, spleen and blood of the protected animals in comparison with the unprotected controls.