c-Fos expression was examined in rat brains at increasing times after a single noxious stimulus to one hindpaw. In some nuclei the expression peaked at 1 h and was gone by 6 h; in others it was biphasic with a larger peak appearing 6 h after the first. In other rats a second, contralateral stimulus was given at increasing times after the first, and c-Fos examined after a further 1.5 h. In some nuclei the first stimulus potentiated c-Fos expression caused by the second stimulus; in others the second stimulus erased any c-Fos still present from the first. Thus two similar stimuli can interact in very different ways in effecting c-Fos expression in different central nervous system nuclei, and rapid down-regulation might represent a novel type of interaction.