Low concentrations of sodium hypochlorite (chlorine bleach) destroyed S antigen on intact fresh red cells (RBCs). At levels of 0.0005 percent sodium hypochlorite in a 3 percent RBC suspension, S+s+ cells immediately became nonreactive with anti‐S. S+s‐ cells required approximately 1.5 times this level of sodium hypochlorite to destroy S antigen reactivity. Anti‐S absorbed three times with treated S+RBCs demonstrated no significant reduction in titer. In addition to its effect on S, the Rh antigens D, C, E, and e appeared slightly reduced in strength after treatment with sodium hypochlorite. However, the c antigen, as well as 20 other red cell antigens tested, appeared unaffected. Osmolality and pH determinations of supernatants from treated and untreated RBCs showed no significant differences. The proposed mechanism of S antigen destruction is an oxidation of the methionine residue in the S determinant. When sodium hypochlorite is used as a disinfectant, it should be rinsed thoroughly from all surfaces that might contaminate solutions that contact test RBCs. The destruction of the S antigen by sodium hypochlorite may be useful in testing complex antibody mixtures when a limited cell selection is available.