The dissemination of Pseudomonas aeruginosa to the bloodstream increases the likelihood of developing fatal sepsis. In experimental models, the ability to disseminate is linked to expression of the exoenzyme S pathway. Genetic and biochemical analysis of the pathway has led to the identification of the two structural genes encoding exoenzyme S, exoS and exoT. A key regulator of several loci of the pathway has been identified as a DNA-binding protein with transcriptional activation properties. Preliminary evidence suggests that exoenzyme S and the Yop virulence determinants of yersiniae share homology among proteins involved in their synthesis and secretion. With the addition of exoS and exoT to the molecular arsenal, questions concerning in vivo toxicity and target specificities of exoenzyme S can be directly addressed.