The effects of r-TNF alpha on cell cycle progression and DNA polymerase activity in Daudi lymphoma cells have been analyzed. Cytofluorimetric analysis of the cell cycle after 6 to 24 hr of treatment revealed both a decrease of BrdU incorporation per cell and a light inhibition of S phase as assessed by the analysis of the percentual distribution of cell cycle compartments. The reduction of BrdU incorporation can be related to the early decrease in the rate of DNA synthesis that follows r-TNF alpha treatment. These results suggest that one of the early events induced by r-TNF alpha at nuclear level is the slowering of DNA synthesis leading to a reduced cell cycle progression.