Each of six healthy volunteers was studied on three different occasions to determine the interactions of placebo–physostigmine, diazepam–physostigmine, and morphine–physostigmine with respect to respiration and psychomotor function. Respiratory measurements were made using the steady state and isohypercapnic techniques. Psychomotor function was assessed by the Trieger Dot Test (TDT) and compared with the Continuous Performance Test (CPT). Administration of physostigmine alone (3 mg, iv) did not affect ventilation. Diazepam (0.29 mg/kg, iv) did not cause a significant depression of ventilation in all subjects, although psychomotor function was impaired as measured by the CPT. The latter was unaffected by physostigmine. Administration of morphine (0.21 mg/kg, iv) caused a significant decrease in ventilation that was not antagonized by physostigmine. Morphine did not impair psychomotor function. The authors conclude that physostigmine is an ineffective antagonist of narcotic-induced respiratory depression and that the CPT correlates well with the TDT.