Cytochrome-oxidase (CO) histochemistry has revealed important functional subdivisions, modules, and processing streams in the macaque visual cortex. The present study is aimed at analyzing the development and characteristics of CO patterns in the human visual cortex by means of histochemistry and immunohistochemistry. At 26 weeks of gestation, both the ventricular and subventricular zones had low levels of CO, while the cortical plate had moderate levels of CO. At birth, supragranular CO-rich zones (puffs) were not clearly organized, indicating that the development of puffs in the neonatal striate cortex lags behind that of the macaque monkey, whose puffs appear weeks before birth. Puffs were more clearly discernible in human cortex at postnatal day 24, and became well organized by the fourth postnatal month. Layer IVc alpha in the neonate exhibited a higher level of activity and amount of CO than the central portion of IVc beta, which contained a dense aggregate of small neurons. The base of IVc beta, however, was often as CO reactive as IVc alpha. In contrast, the majority of specimens available to us from the fourth postnatal month and from adults with no known neurological diseases had significantly greater CO reactivity in layer IVc beta than in IVc alpha. Layer VI was moderately reactive for CO throughout development. In V2, stripes with globular zones of high CO activity were sporadically present at birth, suggesting that their development may parallel or precede that of puffs in V1. These stripes with CO-rich globular zones became more prominent in the adult and radiated orthogonally from the V1/V2 border. They were not, however, clearly organized into alternating thick and thin stripes as they are in the squirrel monkey. Visual cortical areas beyond V2 exhibited high CO activity mainly in layers III and IV and moderate levels in VI, suggesting that sites associated with cortico-cortical pathways may be metabolically most active.