In this report we discuss the role of interferon regulatory factor 1 (IRF-1) in the regulation of ornithine decarboxylase (ODC) transcription during IFN gamma human macrophage activation. We show that a binding sequence for the transcription factor IRF-1 is contained in the first intron of the human ODC gene (from nt +2711 to nt +2722) and we demonstrate that the level of expression of IRF-1 increases in human macrophages and in the human promonocytic cell line, U937, previously differentiated in monocytes/macrophages by phorbol myristate acetate (PMA), after 2 h of IFN gamma stimulation. We also show that the hamster tk-ts13 cell line, stably transfected with the IRF-1 cDNA, over-expresses ODC. In addition, a specific complex was detected, by gel-shift assay after incubating a 20 bp double-stranded oligomer containing the binding sequence for IRF-1 with nuclear proteins extracted from human macrophages and from (PMA-differentiated) U937 cells stimulated with IFN gamma for 2 h.