To determine whether meibomian gland dysfunction can increase tear film osmolarity and produce ocular surface changes analogous to those seen with lacrimal gland disease (keratoconjunctivitis sicca [KCS]), the authors closed the meibomian gland orifices in the right eyes of 11 rabbits by light cautery and studied the changes for 20 weeks. Tear film osmolarity was increased throughout the observation period. Conjunctival goblet cell density and corneal epithelial glycogen levels declined progressively. Closure of the meibomian gland orifices thus increased tear film osmolarity in the presence of normal lacrimal gland function and caused ocular surface abnormalities similar to KCS.