Epimeric 6-amino derivatives of naloxone and naltrexone have been synthesized and the configuration at the C-6 chiral center was determined from NMR studies. All of the derivatives possess narcotic antagonist activity in mice, with each of the 6β epimers having greater potency than the corresponding 6α epimers. In vitro binding experiments indicate that the affinities of these epimers parallel their in vivo potencies. Slight antinociceptic properties were observed with three of the four compounds. The naloxone derivatives 3a and 3b appear to be attractive candidates for investigation as long-acting narcotic antagonists in view of their fourfold greater duration of action relative to the other antagonists (1,2, 4a, and 4b).