Small antimicrobial peptides are abundantly produced by leukocytes. These peptides are active against a broad range of pathogens, notably bacteria, fungi, and enveloped viruses, but hardly anything is known about their physiological and pathophysiological relevance. We observed that bactenecin, a dodecapeptide, is strongly cytotoxic to rat embryonic neurons, fetal rat astrocytes and human glioblastoma cells. This neurotoxicity is unique to bactenecin, as a panel of antibacterial peptides from vertebrates and invertebrates, like defensins, corticostatin, indolicidin, cecropin P1, tachyplesin I, the magainins, or apidaecins did not impair neuronal viability. (C) 1993 Wiley-Liss, Inc.