Thirty-two rabbits with monocular surgically induced keratoconjunctivitis sicca (KCS) underwent masked treatment for 12 weeks with 1 of 4 artificial tear solutions. Disease in each group of treated rabbits was compared with disease in untreated KCS controls. One of the solutions tested was a unique electrolyte-based formulation shown previously to preserve normal goblet-cell density after extended exposure in normal rabbits. Only the electrolyte-based solution decreased elevated tear osmolarity and sodium after 9 weeks of treatment (P < 0.05). At 20 weeks, mean corneal glycogen and conjunctival goblet-cell density in eyes treated with the electrolyte-based solution increased significantly relative to untreated KCS controls (P < 0.01). With the other three solutions, mean glycogen levels and goblet-cell densities were either decreased relative to untreated KCS controls (P < 0.05) or were unchanged. The electrolyte-based solution is the first treatment to increase corneal glycogen and conjunctival goblet cells in a rabbit model of KCS.