Here, we show that recombinant bovine PDE5A1 is pro-teolysedby recombinant caspase-3 inin vitroand transfected Cos-7 cells. In addition, the treatment of PDE5A1-trans-fectedCos-7andPC12cellswithstaurosporine, anapoptotic agent that activates endogenous caspase-3, also induced proteolysis and inactivation of PDE5A1. These findings suggest that there is specificity in the interaction between caspase-3 and PDE5A1 that requires application of an apoptotic stimulus.