This project has developed a clinically useful method (Laser Doppler instrument and its theory of operation) for clinical measurments of microcirculatory blood flow, number density of flowing RBC's, and mean RBC velocity. Assistance has been given to the commercialization of this methodology and its application of clinical research in many labaoratories worldwide. At the NIH our clinical studies have been directed to examining normal and abnormal microvascular dynamics through noninvasive clinical studies (of skin and nasal mucosa) and in intra-operative clinical studies (of muscle and CNS). Collaboration with USUHS is directed at developing endoscopic application of this technology. Considerable theoretical work has been directed toward an adquate construct with which to intercept the physical measurements and refining the accuracy of the microcirculatory measurements. We have discovered abnormal microcirculatory patterns and responses in the skin of patients with sickle cell disease, hypertension, certain cardiac circulatory syndromes, diabetes and skin cancer. The microcirculatory effects of therapy are monitored with this technique in these patients affording a better understanding of the microcirculatory component of these diseases.