A series of 2-methyl-3-carbethoxy-3-(m-hydroxyphenyl)piperidine opiates (13a-d) with N-substituent variations have been synthesized, and their receptor affinities and in vivo agonist and antagonist activities and energy-conformational profiles have been determined. These are racemates of the alpha-epimer at the C-2 position, with a methyl group cis to the 3-phenyl group. One of the main goals of this study was to compare the conformational and pharmacological behavior of these 2-methyl "beta-meperidine" analogues to their 2-desmethyl racemic counterparts (14a-c) previously reported in the literature. The 2-desmethyl and 2-methyl analogues were found to have very similar phenyl equatorial conformers as their lowest energy forms with the addition of a 2-methyl group diminishing conformational flexibility. The presence of the 2-methyl group appears to diminish affinity at the mu-receptor and also to somewhat diminish already weak antinociceptic agonist activity. Given the similarity in lowest energy conformation, this reduction is most likely caused by the unfavorable interaction of the methyl group itself with a local mu-receptor binding site. Superposition of the phenol OH and protonated amine nitrogen NH of either 2-methyl enantiomer of 13a in its lowest energy conformer with the same OH and NH groups of metazocine, used as a high affinity rigid analogue, leads to reasonable overlap. However, the N-substituents and the piperidine and phenyl rings do not overlap in this proposed pharmacophore, perhaps accounting for the rather poor affinities found for these 3-phenylpiperidines and the lack of N-substituent modulation of affinity and efficacy as in fused ring opioids.