The Heidelberg Retina Flowmeter (HRF) is intended to assess ocular blood flow by scanning laser doppler flowmetry. In the retina and possibly in the optic nerve head, carbogen increases blood flow, whereas pure oxygen or high intraocular pressure (IOP) decrease it. This study addresses whether at the papilla of healthy volunteers, the HRF parameter flow, is modulated by breathing 5% carbogen (5% carbon dioxide + 95% oxygen) for 7 minutes, breathing 100% oxygen for 7 minutes, increasing IOP to 50 mm Hg with a suction cup, or decreasing IOP with a single topical ocular instillation of the beta-blockers 0.5% betaxolol (betoptic) or 0.5% timolol (timoptic). At the papilla (20 degrees x 5 degrees, 256 X 64 pixels), values of HRF parameter, flow (50 X 50) pixels, increased after carbogen (N = 5, P < 0.05), but decreased after oxygen (N = 5, P < 0.05) or IOP increase (N = 5, P < 0.01). Although IOP values were significantly reduced by betaxolol (N = 9, P < 0.05) and timolol (N = 9, P < 0.01), HRF values were only significantly decreased (N = 9, P < 0.05) after timolol. In conclusion, at the papilla of healthy volunteers, a positive correlation exists between changes in values of the HRF-parameter, flow, and stimuli considered to modulate retinal and ONH blood flow. Furthermore, although of unkown clinical relevance, it appears that in contrast to betaxolol, values of the HRF parameter, flow, at the papilla of healthy volunteers are significantly decreased after a single instillation of timolol.