The synthesis of a novel series of antitussive agents is described. Two series of amino-substituted tetra- and hexahydrodibenzofurans were prepared and examined for antitussive activity in the guinea pig after cough elicited by electrical stimulation of the vagus nerve. A significant level of activity, comparable with that of codeine, was found in the 4alpha-amino series. The 4-methylpiperazin-1-ylpropionamide (28) was found to be the most active of the compounds synthesized and was equipment with codeine. The effects of structural modification upon antitussive activity were investigated in numerous analogues but no enhancement of activity was achieved over that of 28.