A double-blind, placebo-controlled study was conducted to evaluate the effect of orally administered pilocarpine on unstimulated whole-saliva flow and composition in 28 patients with chronic graft-versus-host disease (cGVHD). Thirteen patients were treated with pilocarpine of 20 mg/ day orally for 7 days, and 15 patients with placebo. Unstimulated whole saliva was collected in the morning on four occasions (30 min before pilocarpine or placebo intake, and 1 h, 1 day and 7 days after the first intake). Significantly, higher salivary flow rates, and sodium and total protein outputs were observed in the second samples of pilocarpine-treated patients compared with controls, whereas calcium and IgA outputs were not altered. Changes in these parameters were not significant in the third and fourth samples, although they were higher in the pilocarpine group. Patients who had received pilocarpine expressed satisfaction with their treatment. These data suggest that pilocarpine may improve salivary flow rate and the feeling of xerostomia in patients with cGVHD.