The c-wave of the human direct current ERG may give new insights about the involvement of the retinal pigment epithelium in hereditary degenerations. In our single-sweep recordings from 236 alert patients we saw reduced c-waves not only in vitelliforme macular degenerations but also in dominantly inherited drusen, Stargardt's disease, cone dystrophies, and x-linked retinoschisis. In achromatopsia the c-wave was close to normal. The relationship of the b- and c-wave, however, was altered only in Best's disease, cone dystrophy, and x-linked retinoschisis. We postulate that the c-wave when more severely reduced than the b-wave reflects not merely the dysfunction of the pigment epithelium but more precisely whether this retinal layer is involved earlier than the photoreceptors.