Papaya ringspot virus-watermelon strain (PRSV-W) affects all agriculturally important species of the Cucurbitaceae, and is of economic interest because of its destructiveness. The objective of this study was to develop a consistent and reliable method to screen watermelon for resistance to PRSV-W. PRSV-W isolates 1637, 1870, 2030, 2038, 2040, 2052, 2169, 2201, 2207, and W-1A were maintained in 'Gray Zucchini' squash, and were used in the inoculations. Three experiments were run, a preliminary experiment to determine the important factors involved in disease development, a main experiment to quantify the effects of those factors, and a retest of three cultigens to determine test variability. The experiment was a split-plot treatment arrangement in a randomized complete block design with four replications. Whole plots were growth stage (cotyledon, first true leaf), subplots were pot size (55 or 100mm), and sub-subplots were the 10 isolates. Plants were rated on a scale of 0-9 for each of three traits: leaf necrosis, mosaic symptoms, and leaf deformation. We found the best method for a screening of the watermelon germplasm collection for resistance to PRSV-W is to grow the seedlings in square, 100mm diameter pots (or 55mm diameter pots if uniform germination is expected) and inoculate plants at the first true leaf stage using PRSV-W isolate 2052 and the rub method. Significant differences were obtained (with LSD values of 0.6-1.5) using four replications of five plants per plot, but fewer replicates and plants may be adequate for a large germplasm screening experiment. The method can be used by researchers interested in screening for PRSV-W resistance in watermelon, verifying that resistance, studying its inheritance, and transferring it to elite cultivars.