We examined the appearance of carbonic anhydrase (CA) activity in rat optic nerves (RONs) 5-77 postnatal days of age and correlated the appearance of enzyme activity with structural and physiological alterations. CA activity was nearly absent before 10 days of age and appeared in this CNS white matter tract with a developmental time-course similar to that of oligodendrogliogenesis and myelinogenesis. When oligodendrocytes and myelin were depleted in the RON by treatment with a mitotic inhibitor, CA activity was markedly reduced. These observations support the hypothesis that CA is contained primarily in oligodendrocytes and myelin. Neural activity in the RON caused changes in extracellular pH (pHo) and the character of these pHo responses was very age dependent; older nerves exhibited much larger acid shifts than neonatal nerves. The development of CA activity may be a factor contributing to this physiological alteration.