This study was conducted to examine the effects of acute doses of lamotrigine (LTG) and carbamazepine (CBZ) in healthy subjects and determine whether the low tendency to impairment with LTG observed in animals applied to humans. Twelve healthy men participated in a placebo-controlled, balanced, double-blind comparison of the drugs on a series of psychomotor, autonomic, sensory, and subjective variables. Variables were analyzed by analysis of variance, and p < 0.05 was considered significant. Adaptive tracking and body sway were impaired by CBZ 600 mg. CBZ 400 and 600 mg impaired smooth pursuit eye movements and also reduced mean peak saccadic velocity. No differences from placebo occurred after LTG. CBZ 600 mg increased heart rate (HR), but no drug-related changes were noted in pupil size, salivary secretion, visual near point, or subjective effects. During the controlled study, mean plasma CBZ concentrations at 2 and 6.5 h after the 600-mg dose were 5.28 and 5.36 micrograms/ml; after LTG 300 mg, they were 3.16 and 3.00 micrograms/ml. Increased CBZ saliva concentrations were significantly associated (p < 0.01) with impaired adaptive tracking, smooth and saccadic eye movements and increased HR, and plasma concentrations were associated with impaired eye movements and body sway.