The authors conducted a double-blind crossover study to determine the effects of physostigmine salicylate on hyperoxic ventilatory response to carbon dioxide (VERCO2) and on awareness in healthy subjects previously sedated with diazepam. Diazepam 0.4 mg/kg iv decreased the slope of VERCO2from 2.41 ± 0.19 to 1.30 ± 0.15 l · min-1± mmHg-1(x ± SEM,P< 0.001). Subsequent injection of physostigmine 2.0 mg iv was associated with a 0.20 ± 0.28 l · min-1· mmHg-1decrease in slope; this was significantly different from the 0.56 ± 0.22 l · min-1· mmHg-1increase in slope associated with saline placebo (P< 0.05). Level of consciousness, on the other hand, increased more after physostigmine than after saline (P< 0.01). The authors conclude that despite an apparent increase in awareness resulting from physostigmine administration, the accompanying decrease in ventilatory drive may contraindicate its use in patients who previously have received diazepam.