Normal peripheral blood leukocytes were tagged with 2, 4-dinitrofluorobenzene at a ratio of 10-11 molecules/cell. One-tenth ml of various concentrations of concanavalin A (Con A) was added to 0.2 ml of either tagged or untagged cells (5 times 10-6/ml) and incubated for 20 minutes at ambient temperature, after which agglutination was scored visually. A readily discernible quantitative difference in the agglutinability of 2, 4-dinitrophenyl (DNP)-tagged versus untagged cells was seen at all concentrations of Con A in the range of 12.5 800 mug/ml. The reaction was maximal at 24 degrees C, somewhat diminished at 37 degrees C, and minimal at 4 degrees C. The agglutination of DNP-tagged leukocytes by 50 mug Con A/ml was completely blocked with 0.1 M methyl-alpha-D-glucopyranoside (alpha-MG), but as low a concentration as 0.001 M alpha-MG inhibited agglutination of untagged cells. The ability of Con A to agglutinate DNP-tagged normal leukocutes may be attributed to a lowering of the zeta potential, a topographic rearrangement of receptor sites, or the formation of new antigenic determinants similar to those found on malignant cells. The last alternative would be consistent with the observation that DNP-tagged normal leukocytes could evoke the production of antibodies that reacted with leukemic granulocytes.