Pseudomonas aeruginosa is an opportunistic pathogen that secretes a number of potential virulence factors. Two of these, exotoxin A and exoenzyme S, catalyze the transfer of the ADP-ribose moiety of NAD to proteins in eukaryotic cells. Exotoxin A catalyzes the ADP-ribosylation of elongation factor 2 (EF-2), leading to disruption of protein synthesis. It has been well characterized and is reviewed elsewhere in this volume. Exoenzyme S has been less thoroughly studied, but several lines of evidence suggest that it might play a role in pathogenesis. In preliminary experiments exoenzyme S appeared to be unselective in choice of substrate proteins, but recent work has shown that it preferentially ADP-ribosylates several of the low-molecular weight GTP-binding proteins. Furthermore, like cholera toxin, exoenzyme S requires a eukaryotic protein for enzymic activity.