The effect of different mixtures of O2 and CO2 on pulsatile ocular blood flow as assessed by laserinterferometric measurement of fundus pulsations was studied. This was done in an effort to identify the gas mixture with an optimal O2/CO2 ratio for treatment in central retinal artery occlusion (CRAO). In a double-blind, randomized, placebo-controlled, six-way cross-over study, 20 healthy young subjects were studied. Fundus pulsation amplitude in the macula (FPAM) and in the optic disc (FPAO), arterialized capillary blood gases, and systemic haemodynamics were measured during baseline and 12 min inhalation periods of 100% O2, mixtures of 2.5%, 5%, 8%, 10% CO2 with oxygen, and air as placebo. The FPAM and FPAO decreased at 100% oxygen (FPAM: -6.2%, P < 0.01; FPAO: -15.1%. P < 0.001), but dose dependently increased with addition of CO2: whereas FPAM was not different versus placebo during inhalation of 2.5% CO2 with oxygen (+0.3%), addition of 5% CO2 and 8% CO2 to oxygen significantly increased FPAM versus placebo (+10.6%, P < 0.01 and +25.9%, P < 0.001, respectively), FPAO was slightly decreased by addition of 2.5% CO2 to oxygen (-2.6%, P < 0.05 versus placebo), 5% CO2 neutralized oxygen's effects on FPAO (+1.5%) and 8% CO2 + 92% O2 significantly increased FPAO (+16.0%, P < 0.001 versus placebo). Inhalation of 90% O2 + 10% CO2 was not tolerated by 19 subjects. Administration of 5% and 8% CO2 with oxygen significantly increased mean arterial pressure. We conclude that addition of 5% CO2 to oxygen is appropriate to maintain or even increase pulsatile ocular blood flow in the macula and optic disc at a level comparable to air-breathing. Addition of higher percentages of CO2 further increases fundus pulsations, with a very steep dose response relationship. Addition of 8% CO2 seems not applicable in patients due to pronounced systemic effects. Hence mixtures of 6 or 7% CO2 with oxygen should be used for further studies in patients with central retinal artery occlusion (CRAO).