The RTX group of exotoxins represents a branch of a family of exoproteins produced by Gram-negative bacteria which share the properties of being secreted by a leader-independent pathway and a tandemly-repeated nine-amino-acid sequence that is responsible for calcium binding. The Escherichia coli hemolysin (HlyA) is the prototype for the RTX exotoxin family which includes the leukotoxins of Pasteurella haemolytica and Actinobacillus actinomycetemcomitans and hemolysins from four Gram-negative genera. A review of the genetics, synthesis, export and target cell reactivity of the E. coli hemolysin is given. An evolutionary tree of the RTX toxin family based on amino acid sequence similarity is presented.