1. The disposition of nalmefene was evaluated in young and elderly normal healthy volunteers. Subjects received either a single 1 mg (n = 18 young; n = 11 elderly) or 2 mg (n = 8 young; n = 15 elderly) intravenous bolus dose of nalmefene. 2. Following the administration of nalmefene, the initial plasma concentrations were significantly higher in elderly vs young subjects. The higher concentrations were the result of the 30 to 40% smaller central compartment apparent volume of distribution that was observed in the elderly subjects as compared with the young volunteers (2.8 +/- 1.1 vs 3.9 +/- 1.11 kg-1 for 1 mg dose). The elderly volunteers also had a significantly shorter distributional half-life (t1/2 lambda 1) than young volunteers (0.7 +/- 0.7 vs 1.3 +/- 0.8 h for 1 mg dose). No significant differences between groups were observed for the elimination half-life, clearance or steady-state apparent volume of distribution. 3. Although transiently higher nalmefene plasma concentrations were observed in the elderly immediately following drug administration, there was no association between this observation and adverse events. We conclude that no dosage alteration is warranted in elderly patients.