We have developed a system to visualize functionally activated neurons and their projections in the brain. This system utilizes a transgenic mouse,fos-tau-lacZ(FTL), which expresses the marker gene,lacZ, in neurons and their processes after activation by many different stimuli. This system allows the imaging of activation from the level of the entire brain surface, through to individual neurons and their projections. The use of this system involves detection of neuronal activation by histochemical or immunohistochemical detection of β-galactosidase (βgal), the product of thelacZgene. Furthermore, the underlying brain state of theFTLmice determines the basal levels of expression of βgal. Here we describe in detail our protocols for detection ofFTLexpression in these mice and discuss the main variables which need to be considered in the use of these mice for the detection and mapping of functionally activated neurons, circuits and regions in the brain.