Two phenotypes exist in the human population with regard to expression of lactase in adults. Lactase non-persistence (adult-type hypolactasia and lactose intolerance) is characterized by a decline in the expression of lactase-phlorizin hydrolase (LPH) after weaning. In contrast, lactase-persistent individuals have a high LPH throughout their lifespan. Lactase persistence and non-persistence are associated with a T/C polymorphism at position -13 910 upstream the lactase gene. A nuclear factor binds more strongly to the T-13910 variant associated with lactase persistence than the C-13910 variant associated with lactase non-persistence. Oct-1 and glyceraldehyde-3-phosphate dehydrogenase were co-purified by DNA affinity purification using the sequence of the T-13910 variant. Supershift analyses show that Oct-1 binds directly to the T-13910 variant, and we suggest that GAPDH is co-purified due to interactions with Oct-1. Expression of Oct-1 stimulates reporter gene expression from the T and the C-13910 variant/LPH promoter constructs only when it is co-expressed with HNF1α. Binding sites for other intestinal transcription factors (GATA-6, HNF4α, Fox and Cdx-2) were identified in the region of the -13 910 T/C polymorphism. Three of these sites are required for the enhancer activity of the -13 910 region. The data suggest that the binding of Oct-1 to the T-13910 variant directs increased lactase promoter activity and this might provide an explanation for the lactase persistence phenotype in the human population.