Chronicity and high therapeutic cost prompted this study to determine a cost-effective and efficacious regimen in treating narcotic-induced constipation. The efficacy of lactulose was compared with polyethylene glycol 3350/electrolyte solution for relief of methadone-induced constipation. This was a randomized, triple cross-over after control run-in (no treatment) study conducted at a methadone maintenance program in Baltimore, Maryland in 57 patients who are affected by opiate-induced constipation. The study was measured by self-reported frequencies, consistency, and ease of defecation during a 1 week run-in control period, followed by 3 treatment phases of 2 weeks each. Polyethylene glycol 3350/electrolyte solution and lactulose produced more "nonhard" stools than the placebo (P < 0.01) and control (P < 0.003). Polyethylene glycol 3350/electrolyte solution produced the loosest stool (P < 0.0001) compared with the control, whereas lactulose had the most adverse effects. There were no significant differences in reducing hard stool formation in either experimental group, but both were better than having nothing or just the placebo. Polyethylene glycol/electrolyte solution resulted in the loosest (diarrheal) stool. It is also likely that polyethylene glycol/electrolyte solution is the most cost effective.