Antimicrobial peptides are produced by nearly all organisms. Certain antimicrobialpeptides from multicellular animals also kill a variety of tumour cells at concentrations notaffecting normal eukaryotic cells. Recently, it was reported that also Plantaricin A (PlnA),which is a peptide with antibacterial activity produced by Lactobacillus plantarum, may killeucaryotic cells. It was shown that PlnA permeabilizes cancerous rat pituitary cells (GH4cells), whereas normal rat anterior pituitary cells are resistant to the peptide. The same studyalso showed that exposure of PlnA to the inside of the membrane, did not lead topermeabilization.This thesis involved three tasks. The first was to examine whether PlnA differentiatesbetween various normal cells, and the second task was to elucidate if the membranepermeabilizing effect of PlnA is restricted to cancerous cells. An examination of thepermeabilizing effect of PlnA on the outer and inner membrane leaflets was the final task. Inorder to examine these questions, we have studied primary cultures of rat liver cells(hepatocytes, endothelial- and Kupffer cells), primary culture of rat kidney cells and twoepithelial cell lines of primate kidney origin (Vero cells from green monkey and humanCAKI-2 cells). The Vero cell line is derived from normal cells, whereas the CAKI-2 cell lineis derived from a cancerous tumour. The membrane effects were studied by means of patchclamp recordings and microfluorometric (fura-2) monitoring of the cytosolic concentrationsof Ca2+ ([Ca2+]i) and fluorochrome.In all of the cells an exposure to 100 500 μM PlnA induced a nearly instantpermeabilization of the membrane, indicated by the following criteria: increased membraneconductance, membrane depolarization, increased [Ca2+]i, and diffusional loss offluorochrome from the cytosol. When exposed to 100 μM PlnA, none of the inside-outpatches from Vero cells were permeabilized. On the contrary, more than 80 % of the outsideoutpatches were permeabilized at 10 μM PlnA. We thus conclude that the permeabilizingeffect of PlnA is not restricted to neither of the normal tested cell types nor the cancerouscells, and that PlnA differentiate between the inner and outer membrane leaflet.