The influence of α and β subunits on the properties of nicotine-induced activation and desensitization of neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopusoocytes was examined. Receptors containing α4 subunits were more sensitive to activation by nicotine than α3-containing receptors. At low concentrations of nicotine, nAChRs containing β2 subunits reached near-maximal desensitization more rapidly than β4-containing receptors. The concentration of nicotine producing half-maximal desensitization was influenced by the particular α subunit expressed; similar to results for activation, α4-containing receptors were more sensitive to desensitizing levels of nicotine than α3-containing receptors. The α subunit also influenced the rate of recovery from desensitization; this rate was approximately inversely proportional to the apparent nicotine affinity for the desensitized state. The homomeric α7 receptor showed the lowest sensitivity to nicotine for both activation and desensitization; α7 nAChRs also demonstrated the fastest desensitization kinetics. These subunit-dependent properties remained in the presence of external calcium, although subtle, receptor subtype-specific effects on both the apparent affinities for activation and desensitization and the desensitization kinetics were noted. These data imply that the subunit composition of various nAChRs determines the degree to which receptors are desensitized and/or activated by tobacco-related levels of nicotine. The subtype-specific balance between receptor activation and desensitization should be considered important when the cellular and behavioral actions of nicotine are interpreted.