Purpose: In this study we investigated the effect of a somatostatin analogue, octreotide, (SMS 201-995) on tear secretion in rats. Method: The animals were anaesthetized intraperitoneally (ip) with urethan (1.2 g/kg) The drugs were injected subcutaneously (sc.). Tear samples were collected by folding a 5 mm section of the Schirmer strip over the lower lid margin to absorb tear fluid from the lower conjunctival sac for 5 mm. Forty animals were divided into four groups (n = 10). Group I (control) received 1 ml of saline, group 2 received 100 mu g/kg of SMS 201-995, group 3 received 50 mu g/kg of acetylcholine (Ach), group 4 received 100 mu g/kg of SMS 201-995 and 30 min later 50 mu g/kg of Ach. At t = 0 the local anesthetic proparacain HCI was instilled onto the ocular surface to minimize reflex secretion. Baseline secretion was measured before administering the various treatments. Results: While Ach alone significantly increased tear secretion, SMS 201-995 reduced it compared to saline (control) (p < 0.0001, p < 0.001, respectively). SMS 201-995 combined with Ach decreased tear secretion compared to Ach alone (p < 0.03). Conclusion: SMS 201-995 significantly inhibits Ach stimulated tear secretion in rats.