Interactions between Potato virus X (PVX) and Potato virus S (PVS) were studied in potato plants, and isolates of PVX were inoculated to potato cultivars from four continents to identify occurrence of PVX resistance genes. Mixed infection with PVX and PVS increased the titer of PVS and enhanced expression of foliar symptoms in primarily and secondarily infected plants of 'Royal Blue'. PVX isolates belonging to strain groups 1 and 3 (WA1+3) or 3 (XK3 and TAS3) were sap and graft inoculated (1 to 3 isolates each) to 38 cultivars and one breeding line. Presence of extreme PVX resistance gene Rx was identified in four Australian ('Auski', 'Billabong', 'Flame', and 'Ruby Lou') and two European ('Mondial' and 'Rodeo') cultivars, and in a clone of North American 'Atlantic'. PVX hypersensitivity gene Nx was identified for the first time in two Australian ('Bliss' and 'MacRusset'), four European ('Almera', 'Harmony', 'Maxine', and 'Nadine'), and one North American ('Ranger Russet') cultivars, and in Australian breeding line 98-10713. PVX hypersensitivity gene Nb was identified for the first time in one Australian ('White Star'), five European ('Innovator', 'Kestrel', 'Kipfler', 'Laurine', and 'Royal Blue'), and one North American ('Shepody') cultivars. Probable ancestral sources of the resistance genes found in different cultivars were identified. Thus, although PVX resistance genes often occur in parents used in crosses, knowledge of their occurrence in parents and cultivars is often lacking. On sap inoculation, systemic hypersensitive phenotypes that caused shoot death often developed in cultivars with Nx but not necessarily in all shoots. This phenotype caused severe necrotic symptoms in infected tubers. In some instances, passage through cultivars with Nb separated strain group 3 from mixed isolate WA1+3.