Changes in the lysosomal enzyme acid phosphatase have been assayed in mouse spleen cells after injection of the animal with various antigens. Disruption by freezing and thawing or sonication of spleen cells or the large granular fraction showed, 48 hours after injection of antigen, an increase in enzyme level irrespective of the antigen used. In contrast, if non-disrupted lysosomes were examined only cells from animals treated with aggregate-free antigen (BSA) showed an increase in level. Spleen cells from animals treated with the other antigens, heat-aggregated BSA, haemocyanin (KLH) and sheep red cells, showed that the enzyme was less accessible to its substrate, reflected by lower levels of enzyme. The results are discussed in relation to possible changes in the stability of the lysosome membrane and the involvement of lymphocytes.