This is part of a continuing patch-clamp study exploring molecular actions of anesthetics and systematically varied related substances on 5-HT3A receptors as prototypes of ligand-gated ion channels. Specifically, n-alkanols, related to but simpler in structure than propofol, were studied to explore the complex actions of this leading intravenous anesthetic. Outside-out patches excised from HEK 293 cells heterologously expressing human 5-HT3A receptors were superfused with even-numbered n-alkanols (ethanol through n-tetradecanol) of different concentrations. Fast solution exchange for varying durations allowed separation of drug actions by their kinetics. Compared with propofol the electrophysiological responses to n-alkanols were not much simpler. n-Alkanols produced fast and slow inhibition or potentiation of current amplitudes, and acceleration of current rise and decay time constants, depending on exposure time, concentration, and chain-length of the drug. Inhibition dominated, characterized by fast and slow processes with time constants separated by two orders of magnitude which were similar for different n-alkanols and for propofol. Absolute interaction energies for ethanol to n-dodecanol (relative to xenon) ranged from -10.8 to -37.3kJmol(-1). No two n-alkanols act completely alike. Potency increases with chain length (until cutoff) mainly because of methylene groups interacting with protein sites rather than because of their tendency to escape from the aqueous phase. Similar wash-in time constants for n-alkanols and propofol suggest similar mechanisms, dominated by the kinetics of conformational state changes rather than by binding reactions.