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The capacity of denatured proteins to provoke anaphylactic sensitivity and delayed sensitivity in guinea pigs has been investigated. It has been found that heat-denatured proteins are as effective as native proteins in provoking delayed hypersensitivity to either material, in spite of the fact that such denaturation greatly modifies their antigenicity from the point of view of antibody production. Pure delayed hypersensitivity, moreover, occurs regularly in response to extremely minute amounts of a good antigen, whether native or denatured. It is further shown that immunological cross-reactivity can be demonstrated regularly by means of the delayed hypersensitivity reaction in guinea pigs, at a time when no cross-reacting antibodies of conventional type can be found. The significance of these observations in regard to the relationship between delayed hypersensitivity and antibody production is discussed. [ABSTRACT FROM AUTHOR]