Phenotypic resistance to chloramphenicol and ampicillin was induced in sensitive Escherichia coli K-12 strains during incubation with the following substances: acetate, acetylsalicylate (aspirin), benzoate, dimethyl sulfoxide, 1-methyl-2-pyrrolidinone, and salicylate. In addition, acetyl-salicylate and salicylate induced resistance to nalidixic acid and tetracycline. The induction of resistance was highly efficient but varied somewhat with the strain and inducer used. In the presence of inducers, from 10% to 100% of the cells formed colonies on antibiotic media, an increase of 10- to 1000-fold over the controls without inducer. After growth in the absence of these inducers, the cells were normally sensitive to the antibiotics. Thus, the resistance was not due to a heritable change. These inducers also increased the level of chloramphenicol resistance of a strain carrying cat (whose gene product inactivates chloramphenicol by acetylation). All of the inducers are chemotactic repellents for E. coli, and they are detected by the tsr gene product (with the possible exceptions of dimethyl sulfoxide and methylpyrrolidinone, whose modes of detection are not known). Nickel sulfate and cobalt sulfate, repellents that are detected by the tar gene product, neither promoted resistance to chloramphenicol nor prevented the induction of resistance by acetylsalicylate. Since several of the inducers are present in common drugs or foods, it may be of medical importance to evaluate their effects on antibiotic therapies.