Effects of age and gender on the pharmacokinetics and pharmacodynamics of ramelteon, a hypnotic acting via binding to melatonin MT1 and MT2 receptors, were evaluated in healthy young (18–34 years) and elderly (63–79 years) volunteers. Part 1 evaluated the pharmacokinetics of open-label oral ramelteon, 16 mg. Part 2 was a double-blind, randomized, 2-trial crossover pharmacodynamic study of 16-mg ramelteon and matching placebo. Ramelteon clearance was significantly reduced in elderly vs young volunteers (384 vs 883 mL/min/kg, P < .01) and half-life significantly increased (1.9 vs 1.3 h, P < .001). Gender did not significantly influence clearance or half-life. Ramelteon was extensively transformed to its hydroxylated M-II metabolite, with serum AUC values averaging about 30 times those of the parent drug. Compared to placebo, ramelteon increased self- and observer-rated sedation, but age and gender did not influence the magnitude of the ramelteon-placebo difference. Ramelteon did not significantly impair digit-symbol substitution test performance or impair information acquisition and recall. Thus, the reduced clearance and higher serum levels of ramelteon in elderly subjects were not associated with enhanced pharmacodynamic effects. The usually recommended clinical dose of ramelteon (8 mg) does not require modification based on age or gender.