The expression of alpha-galactosidase in liver, heart, and brain during postembryonic development has been examined in several inbred mouse strains. In most strains, the developmental patterns of alpha-galactosidase are coordinate with those of two other acid hydrolases, beta-glucuronidase and beta-galactosidase. Certain inbred mouse strains, including members of the C57-C58 family, have a tissue-specific alteration in the temporal expression of alpha-galactosidase activity. This alteration shows additive inheritance and appears to be controlled by a single genetic locus. The altered developmental expression of the enzyme is not accompanied by any discernible change in its physical properties.