The enantiomers of cis- and trans-1,2,3,4,4a,5,10,10a-octahydro-9-hydroxy-1- propylbenzo[g]quinolines (10 and 11, respectively) and the enantiomers of trans-1,2,3,4,4a,5,6,10b-octahydro-10- hydroxy-4-propylbenzo[f]quinoline (12) have been synthesized and their stereochemical and conformational characteristics have been studied by use of X-ray crystallography and molecular mechanics (MMP2) calculations. The compounds, which are conformationally restricted analogues of the potent 5-hydroxytryptamine (5-HT) receptor agonist 8-hydroxy-2- (dipropylamino)tetralin (8-OH-DPAT; 1) have been evaluated for central 5-HT and dopamine receptor stimulating activity by use of biochemical and behavioral tests in rats. In addition, we have evaluated the ability of these compounds and a number of previously reported analogues to displace [3H]-8-OH-DPAT from 5-HT1A-binding sites. The enantiomers of 12 behave as potent 5-HT1A-receptor agonists, whereas the octahydrobenzo[g]quinoline derivatives are much less potent or inactive. In general, the affinities of the compounds correlate well with their agonist potencies. The set of compounds under study is accommodated by a novel computer-graphics-derived model for 5-HT1A-receptor agonism. The model consists of a flexible pharmacophore and a partial receptor-excluded volume.