The aim of this study was to investigate the expression of c-fos protooncogene in normal human peripheral blood leukocytes by Northern blot analysis. Unlike lymphoid cells, monocytes express appreciable levels of c-fos transcripts. Unexpectedly, unlike HL-60 (promyelocytic)-derived granulocytes, freshly isolated polymorphonuclear cells (PMN) showed c-fos expression, with higher levels of expression then monocytes. The expression of c-fos by PMN was superinduced by cycloheximide. When PMN were treated with stimuli known to activate some functional activities of these cells (phorbol esters, inactivated streptococci, colony-stimulating factors, tumor necrosis factor) the expression of c-fos was augmented. The 'constitutive' and inducible expression of c-fos in PMN was also detectable after 20 hours of culture. These data show that, among the cells belonging to the myelo-monocytic lineage, c-fos expression is not restricted to monocytes-macrophages and that data obtained from established cell lines are not necessarily representative of fresh normal cells. c-fos expression in PMN may play a role in the regulation of mature circulating myelocytes.