Before the development of near-infrared spectroscopy (NIRS) for monitoring of hemoglobin and cytochromes in situ, the Jöbsis laboratory designed a visible light reflectance spectrophotometer. The method was not as useful for cytochrome oxidase measurements, which stimulated the search for a better method that culminated in NIRS. Visible light reflectance spectrophotomery was, however, usefully applied in several experimental applications, such as the study of brain capillary hemoglobin saturation during changes in inspired gas mixtures in awake and anesthetized animals, and to record transient increases in total hemoglobin (blood volume) after local neuronal activation by direct cortical electrical stimulation, demonstrating a response that is fundamental to functional magnetic resonance imaging blood oxygen level–dependent methods. A third application of the instrumentation was for brain capillary red cell mean transit time analysis, estimated by recording the passage of a red cell–free bolus through the cerebral cortical optical monitoring field. Taken together with his previous application of fluorescence detection of nicotinamide adenine dinucleotide, the visible and near-infrared spectroscopy demonstrate that Frans Jöbsis was a pioneer in the application of optical techniques to the study of intact organs in situ. These methods have been used to illuminate the basic function of the cerebrovascular and metabolic pathways in both physiological and pathological conditions.