Degradative enzyme activity has been shown to be elevated in many diseases including shock, diabetes, schizophrenia, several types of cancers, and coagulation disorders. The ability to measure degradative enzyme activity in whole blood and other complex samples would be useful for the development of rapid clinical diagnostics, the elucidation of disease progression, and the design of therapeutics. Current techniques to measure degradative enzyme activity require considerable amounts of time and sample processing steps. In this dissertation, a novel method for rapid detection of degradative enzyme activity, specifically protease activity, in whole blood is applied to several disease states: diabetes, schizophrenia, and premature neonates.