The effects of physostigmine on scopolamine-induced changes were investigated in a randomized, double-blind cross-over study utilizing quantitative electroencephalogram (qEEG) and cognitive tasks. Ten healthy male volunteers received scopolamine 0-6 mg subcutaneously. After 90 min, single doses of either 0.5, 1.0 and 2.0 mg physostigmine salicylate or placebo were administered subcutaneously in randomized order. qEEG, cognitive function and the visual analogue scale were recorded before and at 1, 2, 3, 4, 6, and 8 h after scopolamine administration; that was 0.5, 1.5, 2.5, 4.5, and 6.5 h after physostigmine administration. Scopolamine produced an increase in delta (1.25-4.50 Hz) and theta power (4-75-6.75 Hz) in qEEG 1 h after administration compared to baseline, while physostigmine decreased the spectral delta power density in qEEG compared to placebo. The maximal effect of physostigmine was seen up to 1.5 h after injection. A dose-dependent reversal of the scopolamine induced decrements in cognitive performance was found 0.5 h after administration of physostigmine. Psychometric tests sensitively discriminated between the doses of physostigmine, and showed dose- and time-dependent effects. The results suggest that physostigmine may reverse the scopolamine-induced changes in both qEEG and cognitive function. This reversal was temporary and of short duration.