This study was undertaken to see whether long-term locally applied ocular medications produced any alterations in the ocular surface, and, in particular, whether it caused damage to the mucus layer of the tear film. The authors studied the ocular surface of 40 control subjects (group 1), 21 patients (group 2) chronically treated with a commercial preparation of 0.5% timolol maleate, and 20 previously untreated glaucomatous patients (group 3) in need of treatment with the same drug. Parameters studied were Schirmer's test, lacrimal meniscus height, break-up time, fluorescein and rose Bengal stains, conjunctival impression cytology, mucus staining, and the ferning test. Patients in groups 2 and 3 showed a significant decrease (P less than 0.001) in the number of normal Schirmer's and break-up time tests. All had positive vital stains. Results showed a significant decrease (P less than 0.001) in goblet-cell density, mucus granules, and reticular sheets, and an increase (P less than 0.001) in pathologic crystallization patterns. These results demonstrate that chronic application of a commercial preparation of timolol maleate damaged the ocular surface, especially the mucus layer of the tear film.