Retinal pigment epithelium (RPE)-choroid-sclera preparations from black, dutch-belted rabbits were sealed in an Ussing chamber. The RPE-generated trans-RPE voltage (Ve) and electrical resistance (R) were monitored. Epinephrine (an alpha and beta adrenergic agonist) reduced Ve by as much as 39% without affecting R. A response to epinephrine was noted at concentrations as low as 1.4 X 10(-7) M. Phenylephrine (an alpha adrenergic agonist) had essentially the same effect as epinephrine at identical concentrations. Clonidine (an alpha-2 adrenergic agonist) had a very slight effect but only at 10(-4) M. Isoproterenol (a beta adrenergic agonist) had no apparent effect upon Ve or R. The RPE response to epinephrine and phenylephrine was blocked by the alpha adrenergic antagonist phentolamine and by the alpha-1 adrenergic antagonist prazosin but not by the alpha-2 adrenergic antagonist yohimbine or by the beta adrenergic antagonist propranolol. Dibutyryl cyclic AMP (in the presence and absence of IBMX) and cyclic GMP (as cGMP and in the dibutyryl form) had no apparent effect upon Ve or R. These results indicate that rabbit RPE possesses an alpha-1 adrenoreceptor which, when stimulated, substantially reduces the RPE generated trans-RPE electrical current.