Using the modified Lambert-Beer law to analyze attenuation changes measured noninvasively during functional activation of the brain might result in an insufficient separation of chromophore changes (“cross talk”) due to the wavelength dependence of the partial pathlength of photons in the activated volume of the head. The partial pathlength was estimated by performing Monte Carlo simulations on layered head models. When assuming cortical activation (e.g., in the depth of 8–12 mm), we determine negligible cross talk when considering changes in oxygenated and deoxygenated hemoglobin. But additionally taking changes in the redox state of cytochrome-c-oxidase into account, this analysis results in significant artifacts. An analysis developed for changes in mean time of flight—instead of changes in attenuation—reduces the cross talk for the layers of cortical activation. These results were validated for different oxygen saturations, wavelength combinations and scattering coefficients. For the analysis of changes in oxygenated and deoxygenated hemoglobin only, low cross talk was also found when the activated volume was assumed to be a 4-mm-diam sphere. © 2002 Society of Photo-Optical Instrumentation Engineers.