It has been said that Langerhans cells can be induced to migrate into the central cornea by various stimuli. We investigated whether extended wear of hydrogel lenses induced the migration of Langerhans cells into the central cornea. Guinea-pig eyes were fitted with hydrogel contact lenses, and the number of adenosine triphosphatase (ATPase)-positive dendritic cells at the limbus, peripheral, and central corneal epithelium was quantified after 1, 2, 4, and 8 nights of extended wear. The cells were identified with histochemical procedures using ATPase stain. At baseline, ATPase-positive dendritic cells were seen at the limbus and peripheral cornea, with the density decreasing from limbus to peripheral cornea. There were no cells in the central cornea. With extended wear, cells increased in number at the peripheral cornea from 2 nights onward, and cells were seen in the central cornea from 4 nights onward. Extended wear of hydrogel lenses induced migration of ATPase-positive dendritic cells (Langerhans cells) into the central cornea. It is possible that they may play a role in the pathophysiology of some of the adverse events seen with contact lens wear.