Polyamines naturally occur in all living beings and play an important role in the regulation of cell proliferation, differentiation, and functional stimulation of terminally differentiated cells. Our studies, using specific inhibitors of polyamine biosynthesis such as alpha-difluoromethylornithine and methylglyoxal-bis[guanylhydrazone] to prevent polyamine accumulation, have indicated that polyamines are associated with functional activation of human macrophages. Both inhibitors diminished the respiratory burst activity of macrophages induced by lipopolysaccharide and interferon gamma. The methylglyoxal-bis]guanylhydrazone] inhibitory effect was concentration-dependent and could be reversed by spermine, which is the final product of polyamine biosynthesis.