The present study investigated the expression of glycogenin, the protein primer for glycogen synthesis, and the high affinity glucose transporter isoform GLUT3 as a further potential regulator of cellular glycogen metabolism, in first trimester and term human placenta using immunohistochemistry and Western blotting. At term, glycogenin was most abundant in the endothelium of fetal vessels. Trophoblast as well as basal decidual cells were moderately stained. The glycogenin distribution pattern in first trimester placentae resembled that at term, but reactivity was generally less intense. Extravillous trophoblast and villous cytotrophoblast were the major sites of GLUT3 expression. Endothelial cells were also strongly labelled with the GLUT3 antiserum. Western blotting identified both free and glucosylated glycogenin, as well as a 48 kDa band reacting with GLUT3 antiserum in placental villous tissue. Glycogenin immunoreactivity remained unaffected by amylolytic glycogen digestion, although preceding electron microscopical examination demonstrated the presence of glycogen. These data may indicate that placental glycogenin can be recycled from the immature glycogen or that it is located on the surface of the glycogen molecule. In conclusion, the co-expression of glycogenin with GLUT3 might enable glycogen-storing cells to exchange glucose quite effectively according to prevailing metabolic demands of glycogen synthesis or degradation.