Eyes of adult albino rabbits were injected intracamerally with either normal saline or anticoagulated human sickle cell blood to study the effect of hyperbaric oxygen administration on sickle cell hyphema. The administration of two atmospheres of 100% oxygen for 2 hr to the rabbits raised the pO2 of the aqueous humor from a baseline value of 63.5 +/- 12.3 mmHg (mean +/- SD) to 620 +/- 133 mmHg in saline-injected eyes and 503.7 +/- 89.1 mmHg in eyes injected with human sickle cell blood. This rise in pO2 was highly significant (P less than 0.0001). The percentage of sickled cells in the anterior chamber 2 hr after injection decreased from 35.7 +/- 32.4% in rabbits breathing room air to 4.1 +/- 2.8% in rabbits exposed to hyperbaric oxygen for 2 hr. Hyperbaric oxygen can thus significantly raise aqueous humor pO2 values and decrease the sickling of erythrocytes in the anterior chamber and may be of value in patients with sickle cell hyphema.