New 1-phenyl- and 1-(3-chlorophenyl)piperazines containing a 4-[3-(heterocyclic)propyl] fragment were synthesized. It was found that of all the investigated compounds 11b (Ki = 13 +/- 2 nM) and 8b (Ki = 38 +/- 2 nM) were the most active 5-HT1A and 5-HT2A ligands, respectively. Several derivatives (3a, 4a, 8b, 11b, 12b, 13a, and 13b) were selected as good candidates for new, potential antidepressants on the basis of their 5-HT1A/5-HT2A receptor binding profiles.