The diminished basal tear flow in aged individuals is associated with lymphocytic infiltrations and atrophy of the lacrimal ducts and acini. We have investigated the age-related physiological changes to sympathomimetic stimulation of lacrimal tissue from F344 rats to determine if the responses are uniformly diminished as would be expected by glandular atrophy. The quantitative and temporal pattern of protein and peroxidase secretion by lacrimal gland fragments from young (4 month) and aged (24 month) F344 male rats was examined in a perifusion system. Upon stimulation of tissue from young animals with 0.01 mM phenylephrine for 40 min, secretion above baseline levels of protein was 570.8μg/g tissue and of peroxidase was 45.2ΔA. min−1/g tissue. The response of the aged tissue to phenylephrine was not significantly different from that of the young tissue,β-adren-ergic stimulation by isoproterenol (0.01 mM) evoked only a modest secretion of protein and no consistently measurable peroxidase from young tissue. IBMX alone and in combination with isoproterenol (0.1 mM and 0.01 mM respectively) evoked a large secretion of protein, 1345.7μg/g tissue, and a modest secretion of peroxidase, 9.5ΔA.min−1/g tissue by young tissue. The aged tissue, upon stimulation with the combination of IBMX and isoproterenol, secreted significantly less protein and peroxidase than the young tissue. In separate experiments, the production of cAMP was measured. In young tissue, isoproterenol did not cause a measurable increase of intracellular cAMP. IBMX caused a 2–3 fold increase in cellular cAMP which was not increased further by addition of isoproterenol. Thus a lack of uniformity exists in the age-related changes of lacrimal protein secretion in response to sympathomimetic stimulation. If similar changes occur in human lacrimal gland, this suggests a complex etiology of lacrimal disfunction which includes glandular atrophy as well as selective changes in the responsiveness of the remaining tissue.