White pine blister rust caused by Cronartium ribicola is a damaging non-native disease of five-needled pines in North America. Efforts to control the disease and mitigate damage to date have been only somewhat effective. Recent efforts to improve the health of eastern white pine and reestablish the tree as a dominant species in the North Central United States have focused on identification and propagation of disease-free eastern white pine (Pinus strobus) growing in areas with a high incidence of blister rust. Many of these selections have been shown to resist infection following artificial inoculation with C. ribicola. In this study, 13 eastern white pine families derived from controlled pollination of selections previously determined to possess putative resistance as well as susceptible selections were inoculated with C. ribicola. Mortality data from inoculation studies show superior survivability in three families with over 60% of seedlings able to survive the 52 week post-inoculation monitoring period compared to 0-10% survival of the most susceptible families. Primary needles were collected for histological analysis from all inoculated families 4 weeks after inoculation and from selected families 6.5 weeks and 38 weeks after inoculation. Histological observations of infection sites show distinct resistance reactions in the families more likely to survive infection based on mortality data. Analysis of the reactions in susceptible families revealed extensive hyphal colonization of the vascular bundle and adjacent mesophyll cells that appear uninhibited by tree responses. In resistant families, collapsed cells adjacent to infection sites, heavy deposition of phenolic compounds and abnormal cell growth were documented more frequently and appear to play an integral role in the ability of these eastern white pine families to impede growth of C. ribicola in primary needle tissue.