Various cDNAs coding for part or all of human pre-pro lactase-phlorizin hydrolase (pre-proLPH) were transfected into COS cells and the subcellular location of the lactase-related proteins assessed. Only the complete proLPH reached the plasma membrane. LPH without the pro sequence, and a construct containing the pro sequence and the lactase domain of mature LPH, accumulated intracellularly; the pro sequence with no mature domain was secreted. We conclude that the pro sequence is important for LPH to be transported to the cell surface.