Antimicrobial peptides are present in a wide range of species, from protozoa to man, as effector molecules of innate immunity. Several bovine precursors of antimicrobial peptides have recently been identified, as deduced from cDNA, and assigned to the cathelicidin family. Two of these are the proforms of the antimicrobial peptides BMAP-27 and BMAP-28, which share a similar amino acid sequence, structural conformation, and toxic activity toward several bacterial and fungal strains. Here we report that they are cytotoxic to human tumor cells and normal proliferating, but not resting, lymphocytes at concentrations comparable to those microbiocidal. This effect is primarily due to damage of plasma membrane integrity. A more detailed investigation of the U937 cell line revealed that a Ca2+ influx into the cytosol occurs in the early steps of permeabilization. The perturbation of the membrane structure and the Ca2+ influx are followed by programmed death. A similar apoptosis inducing effect is also observed on in vitro activated human lymphocytes.