The present experiments were undertaken to study the effect of exogenous corticosteroids on carbonic anhydrase (CA) activity in fetal erythrocytes. Rabbit fetuses from 24 days of gestation to term (31 days) were injected intraperitoneally with either 0.2 ml of 0.9% saline or 2.5 mg hydrocortisone succinate. Nonoperated, noninjected animals served as controls. Carbonic anhydrase activity measured at 24 hr after injection was increased in the saline-injected group at all ages studies when compared with the noninjected fetuses. A marked increase (2- to 7-fold) in enzyme activity was demonstrated after steroid injection at 24 but not 48 hr after treatment. An increase in CA activity was also demonstrated after incubating fetal erythrocytes for 2, 4, and 8 hr in the presence of hydrocortisone succinate. It is suggested that low CA activity in infants with hyaline membrane disease (HMD) may reflect lack of enhancement by steroid.