Electron paramagnetic resonance (EPR) oximetry can be used to provide direct absolute measurements of pO(2) in living tissue using India ink as an O(2) reporter. In vivo measurements are made using low frequency (1.2 GHz) EPR spectroscopy and surface loop resonators, which enable measurements to be made at superficial sites through a non-invasive (after placing the ink in the tissues) and repeatable measurement procedure. Ongoing EPR oximetry studies in human subjects include measurement of subcutaneous pO(2) in the feet of healthy volunteers to develop procedures that could be used in the treatment of peripheral vascular disease and oximetry in tumors during courses of radiation and chemotherapy, to follow pO(2) so oxygen-dependent therapies can be optimized. In each case, we aim to provide quantitative measurements of tissue pO(2) which will aid physicians in the characterization of disease status and the effects of therapeutic measures, so that treatments can be applied with optimal effectiveness by taking into account the oxygen-dependent aspects of the therapy. The overall goal is to enhance clinical outcomes. Oximetry measurements of subcutaneous tissue on dorsal and plantar foot surfaces have been made in 9 volunteers, with measurements ongoing for each and the longest set of measurements carried out successfully over the last 5 years. Tumor oximetry measurements have been performed in tumor tissues of 10 patients during courses of radiation and chemotherapy. Tumor types include melanoma, basal cell, soft tissue sarcoma, and lymphoma, and measurement sites have ranged from the feet to the scalp. These studies demonstrate the feasibility of EPR oximetry in a clinical setting and the potential for more widespread use in the treatment of these and other oxygen-dependent diseases.