Evidence is presented which supports the hypothesis of protein degradation taking place in macrophages as a part of the presentation of antigen to T lymphocytes. It is postulated that the ability of T cells to recognize both native and denatured forms of the same protein is dependent upon degradation of both forms of the protein to yield the same peptides and thus results in the stimulation of identical subsets of T cells. The occasional observation of a lack of cross-reactivity could result if the native antigen is particularly resistant to the denaturing conditions found within macrophages.