Qualitative resistance to Melampsora larici-populina leaf rust inherited from North American species Populus deltoides did not allow for durable control of this pathogen in interspecific hybrid cultivars. Despite significant levels of strain-specificity, quantitative resistance would exert lower selection pressures on the pathogen populations, and hence could be more durable. Previous studies restricted to a large P. × interamericana (i.e., P. deltoides × Populus trichocarpa) F1 family revealed that the presence of R1, a segregating defeated qualitative resistance gene inherited from P. deltoides, had major beneficial effects on quantitative resistance. The present study was based on 14 F1 families from a 4 × 5 P. deltoides × P. trichocarpa factorial mating design where at least four defeated qualitative resistances segregate 1:1. Even though quantitative resistance assessments were conducted in the laboratory with a M. larici-populina strain able to overcome these qualitative resistances, their presence had a significant effect on the mean level and on the genetic variability for quantitative resistance. One unprecedented result is the identification of a defeated qualitative resistance which presence is associated with lower levels of quantitative resistance. Possible inferences on the nature of the genetic relationship between both resistance types are discussed.