Diphenhydramine (N,N-dimethyl-2-diphenyl-methoxy-ethylamine) [N,N-dimethyl-2-(diphenylmethoxy)-ethylamin] (DPH) is a well-known local anaesthetic and an antagonist of both acetylcholine and histamine. We tested its antibacterial efficacy by means of three different investigation methods, i.e. microcalorimetry, continuous density measurement and the microdilution test to find out the MIC of this compound against various bacteria. DPH inhibits the growth of E. coli and Klebsiella strains at a concentration of 0.18% of Staphylococcus aureus haemolyticus at 0.37%, of Pseudomonas aeruginosa at 0.75% and Streptococcus faecalis strains at 1.5%. The results of microcalorimetry and continous density measurements showed that the addition of 0.2% DPH to a broth with growing bacteria interferes very quickly with cell metabolism and stops further reproduction. The microcalorimetric findings were carried out with Staphylococcus aureus haemolyticus strain No. 13,665 an- the E. coli strain No. 3579.