Indolicidin, a 13-residue antimicrobial peptide isolated from cytoplasmic granules of bovine neutrophils, exhibits activity against Gram-positive and Gram-negative bacteria as well as fungi. Although indolicidin is bactericidal and permeabilizes the bacterial membranes, it does not lyse the bacterial cells. We examined the effect of bactericidal concentrations of indolicidin on the morphology of Escherichia coli cells and found that it induces filamentation. Further investigations showed that indolicidin inhibits DNA synthesis in E. coli cells at concentrations at which RNA and protein synthesis are either partially affected or not affected at all. Since inhibition of DNA synthesis is also known to induce filamentation in E. coli, it appears to contribute to the antimicrobial activity of indolicidin.