In vitro and in vivo assays of the antihistamine potencies of the optically active isomers of pheniramine and its chlor- and brom-subsituted derivatives, have demonstrated that the predominant activity is in the d-isomers and is of the order of approximately two times that found for the respective racemia compounds. An exception to this finding was the observation that both the d- and l-isomers of isothipendyl were less potent than the dl-form. Of three other anti-histamines known to have been resolved, only for one of them (dimeth-pyrindene) was it reported that the l-isomer was the most potent form. Toxicity studies in several animal species and by various routes of drug administration have not distinguished between the lethal or side effect properties of the potent d-isomers and that found for the racemic compounds.