A series of tertiary and and quaternary derivatives of the stereoisomeric amino alcohols tropine and ψ-tropine has been prepared, and its members were tested intravenously for toxicity in the mouse and cat. Evidence for stereospecificity in drug interaction with the intact animals has been gathered from the gross signs of physiologic disturbance, from recordings of brain potentials in the curarized cat, and from measurement of depolarizing strength on chronically denervated muscle in the cat. With the derivatives in which the bridge nitrogen atom is substituted solely with methyl groups, it appears that ψ-isomers ( cis configuration between N and OR groups) are more potent than the corresponding tropine ( trans) isomers. In the mouse, the quaternary methiodides, ethiodides, and tertiary diphenylacetate esters are paralytic agents and/or convulsants. In the intact cat, the quaternary methiodides show neuromuscular involvement, the quaternary ethiodides function primarily as strong tranquilizing agents, and the tertiary diphenylacetates are strong convulsants. Both sets of quaternary derivatives act as weak-to-moderate depolarizing agents on chronically denervated muscle in the cat. In contrast with their behavior in the intact cat, on the curarized animal arranged for electrical recording in the cortex, the predominant effect of the tertiary diphenylacetates given intravenously is depression of activity.