The experiments reported in this article deal with the possible relation of complement (C′) to allergic histamine release from leukocytes of atopic (ragweed-sensitive) persons. The results show that no measurable consumption of C′ occurs during the release reaction. Systems composed of thrice-washed blood cells reconstituted with plasma which has been treated to destroy hemolytic C′ activity have the capacity to release histamine on introduction of ragweed antigen. Hemolytic activity was abolished by heating at 56° C. for thirty minutes (C′ 1 and C′ 2) and by treatment with zymosan (C′ 3) and ammonia (C′ 4). Washed cells resuspended in such plasmas released 73 to 100 per cent as much histamine as cells resuspended in untreated plasma. Blood cells washed three times in heparinized Locke-Ringer solution and resuspended in this fluid are capable of releasing 56 to 84 per cent as much histamine as washed cells resuspended in their own plasma. Extracts of washed leukocytes (some erythrocytes admixed) obtained after freezing and thawing did not show hemolytic C′ activity but, rather, were slightly anticomplementary, which suggests that C′ is not present in such cell extracts but does not rule out the possibility that anticomplementary effects mask its activity. The inhibition of histamine release brought about by iodoacetate is not accompanied by any change in plasma C′ activity.