Retinitis pigmentosa (RP) is an inherited retinal disorder clinically characterized by a pale, waxy optic nerve head, attenuated retinal blood vessels, and bone spicule pigment in the retina. Hemodynamic studies have demonstrated that RP is associated with a reduction in the retinal and choroidal blood flow. Retinal hemodynamic impairment is also present in early stages of RP, and various hypotheses have been advanced as to the cause. The authors studied 20 patients, 12 males and 8 females, aged 26-42 years (mean 35.1 years) and affected by simplex RP. The patients had a visual acuity of 0.9 +/- 0.1, visual field mean defect of -6.52 +/- 3.58 dB, and b-wave electroretinogram amplitude of 260.08 +/- 8.24 microV. An increase in plasma levels of endothelin-1 (ET-1) was found: 1.910 +/- 0.317 pg/mL versus 1.180 +/- 0.210 pg/mL in non-RP controls (p < 0.02). Moreover both an ocular and systemic vascular impairment was detected by means of color Doppler imaging and laser Doppler flowmetry performed during a cold pressor test. We found a correlation between the increase of ET-1 plasma levels in RP and the decrease of peak systolic velocity in the ophthalmic artery (p < 0.03) and in the posterior ciliary arteries (p < 0.006). It is thought that an increase of ET-1 and retinal oxygen levels in RP could lead to vasoconstriction and a decrease of the retinal blood flow, worsening the abiotrophic process.