Defence responses were investigated in two potato cultivars with different levels of resistance to late blight, Russet Burbank (susceptible) and Kennebec (moderately resistant), after inoculation with single isolates representing Phytophthora infestans genotypes US-1 (previously predominant, mildly aggressive) and US-8 (currently predominant, highly aggressive). The accumulation of brown lignin-like materials and an increase in the cell wall affinity to trypan blue 24 h after inoculation were observed in cv. Kennebec inoculated with US-1, but not in Kennebec inoculated with US-8, or cv. Russet Burbank inoculated with either US-1 or US-8. The expression of PAL-1, HMG-2, PR-1 and PR-5 was investigated in three leaf strata (local, proximal and distal) and at different times after inoculation, using SYBR real-time RT-PCR. The activation of these defence-related genes was affected not only by P. infestans genotype, but also by the potato cultivar and the proximity to the inoculation site. These genes were up-regulated earlier in Kennebec than in Russet Burbank and in response to US-1 than to US-8. Over all, the earliest and strongest up-regulation of these genes occurred in Kennebec inoculated with US-1. Furthermore, PAL-1 and HMG-2 were down-regulated at the site of infection while such down-regulation was not observed for PR-1 or PR-5. In parallel, the accumulation level and location of phenolics and rishitin matched those of PAL-1 and HMG-2 transcripts, respectively. These results strongly suggest that changes in either the activation or suppression of defence responses by the pathogen shape the level of susceptibility of potato cultivars to late blight.