The localizing of pathogen (Ceratocystis ulmi) establishment in Dutch elm disease-resistant hosts is hypothesized as the major mechanism of resistance to this disease. Four factors are proposed that, singly or in all possible combinations, could regulate this general mechanism. We tested one of these factors, vessel size and number of contiguous vessels in the functional xylem at the point of natural inoculation. Using 23 selections from the Ulmaceae, we examined a constant area of second-year xylem of 2-year-old twigs. These anatomical data indicate that a correlation exists between increasing disease susceptibility and increasing vessel group size (the product of average vessel diameter and average number of contiguous vessels). Other evidence suggests that lateral pathogen movement is at first confined to the vessel group or groups of initial inoculation. Therefore, in a given limited time period, tylosis production could more effectively block vertical pathogen movement in vessel groups of small size. Relationships between vessel group size and the extent of sapwood discoloration are discussed. Vessel size and arrangement also is discussed in relationship to the resistance reported for young, greenhouse-grown trees. The use of vessel group size is suggested in screening programs for disease resistance. Recent research on oak suggests chemical modification of xylem tissue to lessen elm susceptibility.