Background The authors evaluated the ability of visible tight spectroscopy (VLS) oximetry to detect hypoxemia and ischemia in human and animal subjects. Unlike near-infrared spectroscopy or pulse oximetry (Spo(2)), VLS tissue oximetry uses shallow-penetrating visible light to measure microvascular hemoglobin oxygen saturation (Sto(2)) in small, thin tissue volumes. Methods: In pigs, Sto(2) was measured in muscle and enteric mucosa during normoxia, hypoxemia (Spo(2) = 40-96%), and ischemia (occlusion, arrest). In patients, Sto(2) was measured in skin, muscle, and oral/enteric mucosa during normoxia, hypoxemia (SPo2 = 60-99%), and ischemia (occlusion, compression, ventricular fibrillation). Results: In pigs, normoxic Sto(2) was 71 +/- 4% (mean +/- SD), without differences between sites, and decreased during hypoxemia (muscle, 11 +/- 6%; P < 0.001) and ischemia (colon, 31 +/- 11%; P < 0.001). In patients, mean normoxic Sto(2) ranged from 68 to 77% at different sites (733 measures, 111 subjects); for each noninvasive site except skin, variance between subjects was low (e.g., colon, 69% +/- 4%, 40 subjects; buccal, 77% +/- 3%, 21 subjects). During hypoxemia, Sto(2) correlated with Spo(2) (animals, r(2) = 0.98; humans, r(2) = 0.87). During ischemia, Sto(2) initially decreased at -1.3 +/- 0.2%/s and decreased to zero in 3-9 min (r(2) = 0.94). Ischemia was distinguished from normoxia and hypoxemia by a widened pulse/VLS saturation difference (Delta < 30% during normoxia or hypoxemia vs. Delta > 35% during ischemia). Conclusions: VLS oximetry provides a continuous, noninvasive, and localized measurement of the Sto(2), sensitive to hypoxemia, regional, and global ischemia. The reproducible and narrow Sto(2) normal range for oral/enteric mucosa supports use of this site as an accessible and reliable reference point for the VLS monitoring of systemic flow.