COLISTIN, a polypeptide antibiotic closely related to polymyxin B, has been in use in the United States for approximately three years. Despite the accumulation of considerable clinical experience with this agent, it is still subject to a good deal of controversy. Three topics are at issue: (1) Is colistin actually superior to polymyxin B with respect to antibacterial activity, therapeutic efficacy, and relative lack of toxicity? (2) What is the toxic potential of colistin; is it, in fact, as nontoxic to the kidneys as claimed in some enthusiastic early reports? (3) Should this agent become the drug of choice in gram negative infections, particularly before sensitivity tests are available? It is the purpose of this brief communication to analyze some aspects of these problems and to offer some tentative conclusions. There is little question but that the sulfate salts of both colistin and polymyxin B have remarkably similar activity