The graft-versus-host reaction (GVHR) was induced in developing chick embryos by inoculation of competent allogeneic cells. The enzyme contents and some properties of lysosomes from the host spleens were examined.Lysosomal enzymes were found to increase markedly during the GVHR. Changes also were found in the distribution of the enzymes within subcellular fractions obtained by differential centrifugation. A higher proportion of the enzymes was not sedimented with the particulate fractions, and in addition, the proportion of nonlatent enzyme activity in homogenates was significantly increased.These results could be correlated with those of a cytochemical analysis of acid phosphatase in the spleen during the GVHR. The activity increased markedly and the reaction product was located in small particles, as well as in large vacuoles and inclusion bodies within giant cells. Both granulocytes and mononuclear cells were found with increased amounts of demonstrable enzyme. Many cells showed diffuse staining within their cytoplasm, which suggests that the lysosomes had broken down in these cells.Similar changes in content and properties of lysosomes have been shown to occur in other systems in which phagocytes are active, or are subjected to stress, as with toxins or antibodies. The present findings are interpreted to reflect an extensive mobilization of host phagocytes in the GVHR, both in terms of their appearance, and of their phagocytic activation.