Traditionally, Corydalis tuber has been used for the control of pain including headache, stomach ache, and neuralgia. In the present study, modulation of the Corydalis tuber on glycine-activated ion current in the acutely dissociated periaqueductal gray (PAG) neurons was studied by a nystatin-perforated patch-clamp technique. High concentrations of Corydalis tuber elicited ion current, which was suppressed by strychnine application, while low concentrations of Corydalis tuber reduced glycine-induced ion current in the PAG neurons. Inhibitory action of Corydalis tuber on glycine-activated ion current was partially abolished by treatment with naltrexone, a non-selective opioid antagonist. Application of N-methylmalemide (NEM), a sulfhydryl alkylating agent, also partially abolished the inhibitory action of Corydalis tuber on glycine-activated ion current in the PAG neurons. These results suggest that the inhibitory effect of Corydalis tuber on glycine-activated ion current in the PAG neurons is one of the analgesic mechanisms of the Corydalis tuber.