The effects of propofol, 2, 6-diisopropylphenol, an intravenous general anesthetic, on signal transduction mediated by the rat M1 muscarinic acetylcholine (ACh) receptor (M1 receptor) were examined in electrophysiological studies by analyzing receptor-stimulated, Ca²⁺-activated Cl^--current responses in the Xenopus oocyte expression system. In oocytes expressing the M1 receptor, ACh induced the Ca²⁺activated Cl^- current, in a dose-dependent manner (EC₅₀=114 nM). Propofol (5 - 50 μM) reversibly and dose-dependently inhibited induction of the Ca²⁺-activated Cl^- current by ACh (100 nM) (IC₅₀=5.6 μM). To determine a possible site affected by propofol in this signal transduction, we tested the effects of this anesthetic (10 μM) on the activation of current by injection of CaCl₂ and aluminum fluoride (AlF₄^-). Propofol did not affect activation of the current by the intracellular injected Ca²⁺, or activation of the current by the intracellular injected AlF₄^-. These results indicate that propofol does not affect G protein, the inositol phosphate turnover, release of Ca²⁺ from Ca²⁺ store or the Ca2⁺-activated Cl^- channel. Propofol apparently inhibits the M1 receptor-mediated signal transduction at the receptor site and/or the site of interaction between the receptor and associated G protein.