2'-Pyridine ring substituted analogs of epibatidine were assessed for equilibrium binding affinity, functional potency, and efficacy at rat neuronal nicotinic receptors expressed in Xenopus oocytes. Binding affinities were determined in membrane homogenates from oocytes expressing alpha2beta2, alpha2beta4, alpha3beta2, alpha3beta4, alpha4beta2, or alpha4beta4. Efficacy (relative to acetylcholine) and potency were measured electrophysiologically with oocytes expressing alpha3beta4, alpha4beta2, and alpha4beta4. Hydroxy, dimethylamino, and trifluoromethanesulfonate analogs had affinities too low for accurate measurement. The bromo analog had affinities 4- to 55-fold greater at beta2 than at beta4-containing receptors, modestly greater efficacy at alpha4beta4 than at alpha4beta2, and 5- to 10-fold greater potency at a4beta4 than at alpha3beta4 or alpha4beta2. The fluoro analog displayed affinities 52- to 875-fold greater at beta2- than at beta4-containing receptors, efficacy at alpha4beta4 receptors 3-fold greater than at alpha4beta2 and alpha3beta4, and was equipotent at all receptors tested. The norchloro analog showed affinities 114- to 3500-fold greater at beta2- than at beta4-containing receptors, 2-fold greater efficacy at alpha4beta2 and alpha4beta4 than at alpha3beta4, and 4- to 5-fold greater potency at alpha4beta4 and alpha3beta4 than at alpha4beta2. The amino analog displayed affinities 10- to 115-fold greater at beta2- than at beta4-containing receptors, 3-fold greater efficacy at alpha3beta4 than at alpha4beta2, and 2- to 4-fold greater potency at alpha3beta4 and alpha4beta4 than at alpha4beta2. Although these compounds displayed a variety of differences in affinity, efficacy, and potency, with one exception (binding affinity and functional potency at alpha4beta4 receptors) there were no significant correlations among these properties.