The posttranslational modification of proteins by the addition of an ADP-ribose group is mediated by ADP-ribosyltransferases, which are expressed widely in many eukaryotic tissues, including leukocytes. DNA encoding arginine-specific ADP-ribosyltransferases has been cloned from both polymorphonuclear neutrophil leukocytes and lymphocytes, and their primary structures are widely conserved, particularly in those domains of the enzyme implicated in NAD+ binding and catalysis. In most cases the enzymes are tethered to the outer aspect of the cell surface or are released directly from the cell surface. The protein substrates of some of the ADP-ribosyltransferases have been identified and the catalytic activity of these enzymes has been implicated in several immune responses as well as white cell chemotaxis. This review describes recent significant advances in this field, and it seems likely that additional leukocyte functions, most particularly those linked to the activity of surface integrins, will be assigned to this class of enzymes.