1. A system is described for simultaneously measuring the respiration and the reflectance of a tissue slice and is applied to a study of guinea-pig cerebral cortical slices.2. Reducing bathing medium osmolarity led to a reversible decrease in reflectance of these slices (as well as slices from liver and kidney cortex). In half isotonic solutions reflectance was reduced by 31%.3. Anoxia led to a decreased reflectance which was eliminated if all the Cl was substituted by the larger glucuronate anion.4. It is concluded that slice reflectance is lowered when cellular volumes are increased by water or isotonic solution influx.5. Membrane depolarization effected by ouabain, high (60 mM) K bathing medium, veratridine or repeated electrical pulses led to rapid decreases in reflectance of 25, 27, 31 and 7.5% respectively. Turning off the electrical pulses caused reflectance to return to control values. Reversibility of the chemical effectors was not tested.6. Substitution of Cl by glucuronate abolished the reflectance changes, although it did not inhibit the increased respiration induced by the depolarizing stimuli.7. Tetrodotoxin abolished both the respiratory and reflectance effects of veratridine and electrical pulses but had no effect upon those of high K or ouabain.8. The decrease in reflectance began about 1 sec after initiation of the pulses and was half maximal by 8 sec.9. Titrating reflectance against [K] showed that an increase of 5 mM-K led to a 4% decrease in reflectance and that reflectance became minimal between 60 and 80 mM-K(+).10. It is concluded that membrane depolarization in excitable cells of the cerebral cortex (and also, possibly, in the glia) causes rapid increases in cell volume due to influx of isotonic solution.11. The results indicate, more specifically, that changes in intercellular K concentrations of size and duration thought to occur following nervous activity in the C.N.S. cause cell volume changes large enough to drastically reduce the intercellular volumes and so, transiently, increase extracellular molecular and ionic concentrations. Increases of extracellular [K] and [Ca] have significant effects upon synaptic transmission and upon spontaneous nervous activity. It is suggested that nervous activity in one cell (or portion of it) might, in this way, strongly influence function in neighbouring elements.