The conformational distributions and Cone-Inverted Cone (Cone') interconversions of monomethoxy-, 1,2-dimethoxy-, 1,3-dimethoxy-, and trimethoxycalixarenes 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 rotating 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)=1,3-dimethoxy- (30.3 kcal mol-1) > trimethoxycalixarene (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.