A lattice of high oxidative metabolic activity occurs in the intermediate gray layer of the human, monkey, and cat superior colliculus. It is composed of a matrix of high enzyme activity that surrounds pale islands or bands of lower activity. In the human the pale bands are 300-400 micron wide while in the smaller colliculi of the monkey and cat they are 100-200 micron wide. The lattice was demonstrated by studying either cytochrome oxidase or succinate dehydrogenase. In the cat and monkey the lattice occurs at the same depth as the lattice of intense acetylcholinesterase activity, but the two lattices are not in spatial register. In the human the lattice of high oxidative metabolic activity is in the middle of the intermediate gray layer, whereas the lattice of intensely stained cholinesterase activity is at the base of this layer, but again the two lattices are not in spatial register. However, in the middle of the intermediate gray layer of the human, there are elongated islands and bands of very low acetylcholinesterase activity that coincide with the pale islands and bands of low cytochrome oxidase activity. An additional lattice of high enzyme activity occurs based on the enzyme nicotinamide dinucleotide phosphate (reduced form)-diaphorase. This lattice is prominent in the cat, occurs more faintly in the monkey, but did not appear to be present in the human. In the intermediate gray layer it had a high degree of overlap with the acetylcholinesterase lattice. The lattice of high oxidative metabolism contains loosely knit clusters of large multipolar cells containing high cytochrome oxidase activity and these cells do not occur in the pale islands. By contrast the cell bodies in the intermediate gray layer that contain either acetylcholinesterase or the diaphorase occur both between and within the patches of corresponding, high enzyme activity. It is suggested that the acetylcholinesterase and diaphorase lattices are mainly associated with afferent fibers while the lattice of high oxidative metabolism is mainly associated with intrinsic cells. The lattices occur in all mammals studied to date and appear to represent a fundamental principle in the organization of the mammalian colliculus. It is concluded that the lattices will provide a useful basis for further studies of the relationship between the many afferent and efferent modules thought to exist in this structure.