A comparison has been made of the release of histamine from tissues of conventional rats, induced by injections of antigen, concanavalin A and clinical dextran, with that from rat isolated peritoneal mast cells. Concanavalin A was less active than dextran when injected into the skin or paws, but the reverse was found when the substances were tested on isolated cells. Similar results were obtained when a pure line of rats relatively resistant to dextran was used, concanavalin A being much more active on isolated cells than on intact mast cells. Antigen was equally active in the two types of rat. It is important, therefore, to state the experimental conditions when comparisons of the activities of histamine releasers are being made.