A composite template for angiotensin converting enzyme (ACE, EC 3.4.15.1) inhibitors and a hypothetical model of the active site of neutral endopeptidase (NEP, EC 3.4.24.11) have been constructed and used to guide the design of dual ACE/NEP inhibitors. For the ACE template, a new computer program was used to flexibly superimpose potent, conformationally restricted ACE inhibitors. This program, which only considers the structures of the ligands, generated three possible templates. It was possible to evaluate the plausibility of these templates because new X-ray data is extending our knowledge of the binding of ligands to zinc metalloproteases. We have found that the available X-ray structures of inhibitors complexed to different zinc metalloproteases share certain conformational features.