Human cytomegalovirus (HCMV) protease is a viral serine protease essential for proteolytic processing of the assembly of protein precursor during cytomegalovirus capsid maturation. Inhibitors to this protease may potentially be useful as antiviral agents for treating HCMV infection in transplant and immunocompromised patients. An X-ray structure of the HCMV protease catalytic domain apo enzyme was solved at Agouron and published in Cell, 86:835-843 (1996). We are taking the structure-based drug design approach to design inhibitors. Using the intense synchrotron X-ray beam we can obtain high resolution diffraction data of inhibitor complexes. The structure information will help to rationalize the structure-activity relationships of inhibitors and will aid the design and optimization of new inhibitors against herpesvirus proteases.