Colisan has the formula Lys3Va14Leu311eTyr and a molecular weight of approximately 1500. The peptide is highly resistant to hydrolysis by proteolytic enzymes (pepsin and trypsin). The t-amino groups of lysine are indispensable for biological activity, since either deamination or acetylation completely inactivates Colisan. A comparative study with basic peptides like polylysine demonstrated their similarity of action, on one hand, and an antagonistic effect to Colisan, on the other. The fast action of the antibiotic and the specific effect on the cell membranes of many different biological systems (Entameba, Paramecium, erythrocytes, smooth muscle, and others) support the hypothesis that the primary damage occurs in the membrane with consequent alteration of permeability. The leakage of intracellular material (histamine) from mast cells after application of Colisan is in accord with this hypothesis. The results strongly suggest that the biological activity of the peptide is based essentially, but not exclusively, on its basic character.