New 1,6-disubstituted trans-decahydro-1,6-naphthyridines were synthesized by stereoselective nucleophilic addition of hydride and cyanide ions to 1,2,3,4,5,6,7,8-octabydro-1,6-naphthyridines, and their predominant conformations were determined. Some trans-decahydro-1,6-naphthyridine derivatives were found to exhibit anti-HIV activity.