Potato leafroll virus (PLRV) causes one of the most serious aphid-transmitted diseases affecting yield and quality of potatoes, Solanum tuberosum (L.), grown in the United States. The green peach aphid, Myzus persicae (Sulzer), is considered to be by far the most efficient vector of this virus. Even the most strict aphid control strategy may not prevent the spread of PLRV unless measures also are taken to keep virus source plants within and outside the crop at a minimum. Hairy nightshade, Solanum sarrachoides (Sendtner), is one of the preferred weed hosts for green peach aphid. The potential of this weed as an aphid reservoir and virus source and its spread or perpetuation were investigated. With the use of double antibody sandwich enzyme-linked immunosorbent assay, it was confirmed that green peach aphid can transmit PLRV to hairy nightshade and that aphids can become viruliferous after feeding on infected hairy nightshade plants. Transmission from hairy nightshade to potato is 4 times the rate of potato to potato or potato to hairy nightshade. The green peach aphid preferred hairy nightshade over potato plants and reproduced at a higher rate on hairy nightshade than on potato. Therefore, a low level of PLRV–hairy nightshade infection could enhance the disease spread in the field.