The effects of the stable cyclic adenosine monophosphate analogue adenosine 3',5'-cyclic monophosphorothioate Sp-isomer (Sp-cAMPS) on the direct-current electroretinogram and the standing potential of the eye were studied. Corneal recordings were obtained from unilaterally vitrectomized albino rabbit eyes during alternating intravitreal perfusions with Sp-cAMPS and a control solution (Pharmacia eye irrigating solution). The contralateral eye was used as a control. To evaluate further the effects on the c-wave, in vivo intraretinal microelectrode measurements were made during simultaneous intravitreal perfusion of Sp-cAMPS and irrigating solution, respectively. Sp-cAMPS in concentrations of 1, 10 and 100 microM was tested by corneal direct-current electroretinography. There was no significant effect on the a-wave amplitude. The b-wave amplitude was reversibly elevated at an Sp-cAMPS concentration of 100 microM was tested by corneal direct-current electroretinography. There was no significant effect on the a-wave amplitude. The b-wave amplitude was reversibly elevated at an Sp-cAMPS concentration of 100 microM (p < 0.01, n = 7). The c-wave amplitude was reversibly elevated at an Sp-cAMPS concentration of 100 microM (p < 0.01, n = 7). The c-wave amplitude was reversibly elevated at a concentration of 10 microM (p < 0.001, n = 8), and this effect was more pronounced at 100 microM (p < 0.001, n = 7). The SP increased reversibly at a concentration of 100 microM (p < 0.001, n = 7). Microelectrode recordings were performed with Sp-cAMPS at a concentration of 100 microM. The recordings showed significant increases in both the transepithelial potential (p < 0.01, n = 3) and the slow PIII (p < 0.01, n = 3). The effects of Sp-cAMPS on the b-wave as well as the two components of the c-wave suggest influences on both the inner retina and the retinal pigment epithelium of the rabbit eye.