Apoptosis provides a mechanism for clearance of unwanted cells in a variety of situations in which programmed or physiological cell death occurs; but the premature death of defensive cells could promote infection, inflammation and concomitant diseases. Polymorphonuclear cells (PMN) of gingival sulcus play an important role in host defense against periodontal tissue-invading bacteria, but their phagocytic activity is conditioned by several virulence factors released by oral pathogens. Polyamines derived from oral bacteria frequently occur at concentrations approaching 1 mM in gingival fluid at diseased periodontal sites. Brief exposure of PMN to polyamines shortened the lag culture time required to observe microscopical or DNA fragmentation traces. Increase of Fas/Apo-1 expression and caspase-8 and caspase-3 activation focused two typical steps in the pathway of the pro-apoptotic mechanism exhibited by polyamines, even if to a different extent: spermine > spermidine > putrescine. The possible role played by polyamines in the pathogenesis of periodontal disease by dysregulating apoptosis of gingival PMN is discussed.