The 6-oxa analogues of potent dopamine agonists, hexahydronaphthoxazines (4a,4b), have been tested for dopamine receptor binding and stimulating activity and were found to be almost inactive. pKa value determinations indicated that these compounds are protonated to approximately 2%, while potent compounds are protonated to a much greater extent. These results strongly support the assumption that the protonated form of DA agonists is the active species at the receptor.