Acid-addition salts of tricyclic isoquinolines 2a/b, 3a/b, 4a-4c, 5, 6a/b, 7, 8a/b, 9a/b, and 17a/b were studied by high-field 'H N M R in CDCll solution. Cis (e.g., 14 and 15 in Figure 1) and trans (e.g., 13) B-C ring-fused structures were identified by using the vicinal 3J(CH-NH) coupling constants, which demonstrate a Karplus-like behavior. In some cases, we initially observed a trans form, which converted to a cis A form by N H proton exchange. For 4c.HBr, the exchange process was slowed by addition of trifluoroacetic acid. In many cases, cis A and cis B structures were preferred in solution. The pendant phenyl group exerted a strong influence on the preferred solution structure. Observation of the initial, unstable trans-fused structures was related to their capture in the solid state and release intact on dissolution. X-ray diffraction was performed on the HBr salts of 2a (B-C cis), 2b (B-C cis), and 4c (B-C trans). The result for 4c.HBr confirmed the connection between the initial trans form in solution and the solid state. For 17b.HCI two conformers, associated with hindered rotation about the bond connecting the 2,6-disubstituted phenyl group to the tricyclic array, were detected at ambient probe temperature; however, rotamers were not observed for either of the two forms (trans and cis A) of I7a.HBr. Two conformers were also found for 16bqHBr. Temperature-dependent behavior was recorded in the 'H NMR spectra of 17b.HBr and 16b.HBr; the activation free energy for interconversion of conformers was estimated to be in the vicinity of 17 kcal/mol for the former and 14-15 kcal/mol for the latter. The 'H N M R spectrum of butaclamol hydrochloride (20.HC1), a potent neuroleptic agent, in Me2SO-d6 revealed two species in a ratio of 81:19, which were assigned as trans and cis A forms, respectively. 'H N M R data for various free bases are also presented and discussed. Empirical force field calculations on three model hydrocarbons are discussed from a perspective of finding an explanation for the configurational/conformational behavior of the bridgehead ammonium salts. Diverse literature examples of structures for protonated bridgehead amines are also discussed. A tentative rationale is suggested for the preference of cis A forms in some protonated tetrahydroisoquinoline derivatives.Although substantial information has been acquired on the structural and conformational properties of alicyclic amines with nitrogen a t the bridgehead position, such as bicyclic [m.n.O] compounds where m and n = 3 or 4, the corresponding protonated