The list of patho-physiological conditions associated with the over-production of super oxide anion expands every day. The most exciting realization is that there appears to be a commonality to the tissue injury observed in various disease states; and that superoxide anion, produces tissue injury (and associated inflammation) in all tissues in similar ways. Tissue injury and inflammation form the basis of many disease pathologies: ischemia and reperfusion injuries, radiation injury, hyperoxic lung damage, atherosclerosis and so forth. This commonality provides an unique opportunity to manipulate numerous disease states with an agent that removes superoxide anion. Much of the knowledge that has been gleaned concerning the roles of superoxide anion in disease has been gathered using the native superoxide dismutase enzyme and, more recently, by data generated in transgenic animals that over-express the human enzyme. Although, the native enzyme has shown promising anti-inflammatory properties in both preclinical and clinical studies, in a variety of diseases, there were drawbacks and issues associated with the use of the native enzymes as therapeutic agents and as pharmacological tools. Based on the concept that removal of superoxide anion modulates the course of inflammation, we have pursued the concept of designing synthetic, low molecular weight mimetics of the superoxide dismutase enzymes that could overcome some of the limitations associated with the use of the native enzyme. The rational design and synthesis of low molecular weight catalysts which mimic a natural enzymic function has potential for use as human pharmaceuticals. Such synthetic enzymes (synzymes) have as a potential utility the treatment of diseases characterized by the overproduction of a potentially deleterious molecule or foreign gene product. The development of manganese(II)-based superoxide dismutase (SOD) mimics and their potential utility as human pharmaceutical agents is described.