Rat alpha 2u-globulin and the mouse major urinary proteins (MUP) are encoded by homologous multigene families whose members exhibit diverse tissue-specific, developmental, and hormonal controls of expression. Although their patterns of expression and hormonal control appear to be very similar in many respects, we have found high levels of alpha 2u-globulin mRNA in rat preputial glands, whereas MUP mRNA could not be detected in the male mouse preputial gland. Male and female rat preputial have similar concentrations of alpha 2u-globulin mRNA, suggesting an absence of endocrine regulation as occurs in the liver and lachrymal glands. Two-dimensional polyacrylamide gel electrophoresis of proteins encoded by hybrid-selected alpha 2u-globulin mRNA indicates that the liver and lachrymal translation products have different mobilities. However, many of the preputial gland products comigrate with most or all of the liver and lachrymal products. Among the possibilities suggested by these results is that alpha 2u-globulin genes expressed in liver and lachrymal glands under endocrine control are also expressed constitutively in the preputial gland.