Clustering of diseases has been appreciated by health insurers and epidemiologists for some time. Co-morbidity suggests shared pathways of disease. It is by now well agreed that common diseases have a strong genetic component. Here we present evidence that the angiotensin I-converting enzyme (ACE) deletion/deletion (D/D) genotype is associated with a large number of common adult diseases, including cardiovascular disease, cancer, and psychiatric disease. Since the ACE D/D genotype has been shown to be associated with increased levels of tissue ACE expression at the protein level, these data suggest that overactivity of ACE may be involved in the pathogenesis of common diseases, as well as the utility of effective ACE inhibition in their treatment and, perhaps, prevention.