TheCPBgenes of the protozoan parasiteLeishmania mex-icana encode stage-regulated cathepsin L-like cysteine pro-teases that are important virulence factors and are in a tandem array of 19 genes. In this study, we have compared the substrate preferences of two CPB isoforms, and CPB3, and a H84Y mutant of the latter enzyme, to analyse the roles played by the few amino acid differences between the isoenzymes in determining substrate specificity. CPB3 differs at just three residues (N60D,D61Nand D64S) in the mature domain. .