Pilocarpine, a muscarinic-cholinergic agonist drug, has been reported to stimulate salivary flow in patients with salivary gland dysfunction. Previous studies involved heterogeneous groups of patients with salivary gland dysfunction and examined the short-term, single-dose, tablet form of pilocarpine. In this single-blind, placebo-controlled study we examined the long-term effects of pilocarpine administration on patients with definitively diagnosed Sjögren's syndrome (SS). Nine subjects with SS who received pilocarpine, and nine age- and sex-matched SS control subjects who received a placebo, participated. Baseline predosing sialometric and clinical data were obtained for all subjects. The study group used 2% pilocarpine as a liquid ophthalmic drop preparation, four drops three times per day, for 6-weeks. Identically appearing placebo solution with the same dosing schedule and duration was used for the control subjects. Sialometric and clinical examinations were performed. The results indicated a significant overall increase in both whole unstimulated salivary flow (0.15 +/- 0.03 ml/min in study subjects vs 0.02 +/- 0.001 ml/min in control subjects; p less than 0.001) and parotid stimulated salivary flow (0.14 +/- 0.04 ml/min in study subjects vs 0.009 +/- 0.002 ml/min in control subjects; p less than 0.001) in the pilocarpine group as compared with the placebo group. The results of this study support the use of pilocarpine to increase salivary flow in patients with SS.