Plants infected with a severe strain of zucchini yellow mosaic virus (ZYMV-CA) produced fewer marketable fruit than non-infected control plants or plants infected with a mild strain of ZYMV (ZYMV-WK); cross protection conserved marketable yield by nearly 75%. Cantaloupe plants in the non-infected control treatment and plants infected solely with ZYMV-WK produced similar numbers of marketable fruit. In another study, ZYMV-WK was introduced successfully into cantaloupe plants using standard agricultural spray equipment at 2.1 kg cm−2 pressure. Infection with the mild strain was related directly to the concentration of virus in our sprays. The highest infection rate (77%) was achieved with a 10% solution of fresh tissue in buffer. Lower percentage solutions, 2 and 1%, resulted in 27.5 and 25% infection, respectively. A 10% spray solution made from frozen infected tissue resulted in 56% infection. Our studies demonstrate the effectiveness of cross protection in cantaloupe and offer a method to growers for applying this technology to large-scale, direct-seeded agriculture.