Pilocarpine induces a profuse flow of saliva when administered orally, but effects on drug-induced oral dryness have not been examined. The aim of this trial was to investigate if pilocarpine increases production of saliva in individuals suffering from dry mouth due to treatment with opioids. Sixtyfive individuals were enrolled in a randomized, double-blind, placebo-controlled trial. The subjects received tramadol (50 mg t.d.s.) to induce oral dryness, and were thereafter assigned to one of three groups. Secretion rate of saliva was measured before and after tramadol, and after the oral administration of pilocarpine (5 mg), placebo, or no treatment. Baseline characteristics did not differ among the groups (mean ± SEM: 0.37 ± 0.06 mL/min), and tramadol lowered the secretion at the same level in all groups (0.15 ± 0.02 mL/min). Pilocarpine increased the flow above that observed with placebo (0.66 ± 0.19 vs. 0.15 ± 0.02 mL/min). Thus, pilocarpine re-establishes the flow of saliva in the state of tramadol-induced oral dryness.