The actions of the cis- and trans-isomers of metanicotine were observed on isolated rabbit aortic strips and ileal segments. The data are interpreted as showing a nicotine-like action on these preparations for both cis-metanicotine and trans-metanicotine. This hypothesis is supported in part by the demonstration that the action of the metanicotine isomers was affected by hexamethonium, cocaine, phenotolamine, reserpine and atropine in a manner similar to that previously seen in studies with nicotine. In dose-response studies on the aortic strip, trans-metanicotine was significantly less active than nicotine. cis-Metanicotine in turn was less active than trans-metanicotine and nicotine. Additionally, four pyridino compounds, 3-pyridylacet acid, N-(3 pyridlyacetyl) glycine, nicotinuric acid and trans-4-(3-pyridyl)-3-butenoic acid, were tested for both agonist and antagonist activity. No stimulatory activity was found with these compounds in either the aortic strip or ileal preparations. In aortic strip preparations, pretreatment with either 3-pyridylacetic acid or N-(3-pyridylacetyl) glycine provided a moderate to marked reduction in the contractile response to trans-metanicotine, whereas pretreatment with trans-4-(3-pyridyl)-3-butenoic acid caused a slight reduction.