Paneth cell secretion of the mouse intestine is an acidic mucopolysaccharide-protein complex, and amino, acylamido carboxyl and phenolic groups of protein were localized to the characteristic granules. It was the purpose of this study to investigate the use of various fixatives in attempting to localize sulfhydryl and disulfide groups of protein to the Paneth cell granule. Pieces of small intestine, 17cm from the pylorus, were removed and fixed in one of the following fixatives: trichloroacetic acid, Carnoy''s, acetone, absolute ethyl alcohol, 10% neutral buffered formalin, Romeis''s, Bouin''s and Zenker''s solution. Tissues were embedded in paraffin and sectioned at 3[mu]. Sulfhydryl and disulfide groups of protein were identified by the technique described by Barrnett and Seligman. Sections of tissue fixed in trichloroacetic acid, Carnoy''s, acetone, alcohol, or Bouin''s fluid did not demonstrate stained granules. Sections fixed in formalin, Zenker''s and Romeis''s solution did reveal stained granules. The results of this study indicate that sulfhydryl and/or disulfide groups of proteins must be included in the chemical description of the Paneth cell secretion.