Two 2,3-dihydrobenzofuran analogues of hallucinogenic amphetamines were prepared and evaluated for activity in the two-lever drug-discrimination paradigm in rats trained to discriminate saline from LSD tartrate (0.08 mg/kg) and for the ability to displace [125I]-(R)-DOI [( 125I]-(R)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane) from rat cortical homogenate 5-HT2 receptors. The compounds, 1-(5-methoxy-2,3-dihydrobenzofuran-4-yl)-2-aminopropane (6a) and its 7-brominated analogue 6b, possessed activity comparable to their conformationally flexible counterparts 1-(2,5-dimethoxyphenyl)-2-aminopropane (3) and its 4-bromo derivative DOB (5), respectively. The results suggest that the dihydrofuran ring in 6a and 6b models the active conformation of the 5-methoxy groups in 3 and 5. Free energy of binding, derived from radioligand displacement KA values, indicated that addition of the bromine in either series contributes 2.4-3.2 kcal/mol of binding energy. On the basis of surface area of the bromine atom, this value is 2-3 times higher than would be expected on the basis of hydrophobic binding. Thus, hydrophobicity of the para substituent alone cannot account for the dramatic enhancement of hallucinogenic activity. Although this substituent may play a minor role in orienting the conformation of the 5-methoxy group in derivatives such as 4 and 5, there appears to be some other, as yet unknown, critical receptor interaction.