The conformational distributions and Cone --> Inverted Cone (Cone＇) interconversions of monomethoxy-, 1.2-dimethoxy-, 1,3-dimethoxy-, and trimethoxycalix[4]arenes 3a-6a were investigated by molecular modeling, The calculated conformational distributions are generally in accordance with NMR data obtained for the p-tert-butyl derivatives 3b-6b. Careful examination of all possible inversion pathways showed that the high inversion barriers of Cone --> Cone＇ interconversion are caused by the cooperative barriers of hydrogen bonds rupture and the steric barrier of relating a methoxy group through the annulus. This cooperative effect is so strong that the Cone --> Cone＇ conversion is blocked at room temperature. The order of the calculated barriers for the Cone --> Inverted Cone interconversions is monomethoxy-(35.1 kcal mol(-1)) > 1,2-dimethoxy-(32.2 kcal mol(-1)) approximate to 1,3-dimethoxy-(30.3 kcal mol(-1)) > trimethoxycalix[4]arene (27.0 kcal mol(-1)), values that are in good agreement with the available qualitative experimental results. The rate-limiting step involved in all cases is the rotation of a methoxy-bearing ring.