Rifarnpicin and trimethoprirn, acting alone, showed high antibacterial activity and broad spectra against 386 strains taken from 9 genera (15 species) of common hospital pathogens. When tested in combination against 304 of these strains, using a method that allows quantitative analysis of the interaction, synergism or addition was almost always observed. The best synergistic action was against streptococci and strains of Proteus spp. The effect was also synergistic or additive against all strains of Kiebsielia aerogenes, Escherichia coli, Enterobacter spp., Pseudonwnas aeruginosa, Bacteroides fragilis and Salmonella typhlmurium which were tested. Only in the case of Staphylococcus aureus was some antagonism observed, but this occurred only at very low concentrations of rifampicin. In the presence of sub-inhibitory levels of trimethoprim the incidence of rifampicin-resistant mutants was decreased. In view of these extremely encouraging and consistent results, we regard the combination of rifampicin and trimethoprim as of sufficient potential to warrant further investigation.