An investigation of M3O13 unit ("M-3 cap") isomerization in the classical polytungstodiphosphates alpha- and beta-P2W18O626-has been undertaken because cap isomerism is an important and structurally well-studied phenomenon in many polyoxometalate families. The relative thermodynamic stabilities of the alpha (more stable) versus beta isomers were established both in the solid state by differential scanning calorimetry (4.36 +/- 0.64 kcal/mol) and in solution by P-31 NMR (3.80 +/- 0.57 kcal/mol). The isomerization of beta-P2W18O626- to alpha-P2W16O626-, followed by P-31 NMR, has a bimolecular rate constant k(2) of 9.3 x 10(-1) M-1 s(-1) at 343 K in pH 4.24 acetate buffer. Several lines of evidence establish the validity of suggestions in the literature that isomerization goes through a lacunary (defect) intermediate. First, the rate is proportional to [OH-]. Second, isomerization increases at higher ionic strengths, and a Debye-Huckel plot is consistent with a rate-limiting reaction between beta-P2W18O626- and OH- (two species with a charge product of 6). Third, alkali-metal cations stabilize the bimolecular transition state (K+ > Na+ > Li+), consistent with recent ion-pairing studies in polyoxometalate systems. Fourth, the monovanadium-substituted products alpha(1)- and alpha(2)-P2VW17O627- (V-51 NMR delta -554 ppm) form during isomerization in the presence of VO2+. The known lacunary compounds (alpha(1)- and alpha(2)-P2W17O6110-) also react rapidly with the same vanadium precursor. Fifth, solvent studies establish that isomerization does not occur when OH- is absent. A mechanism is proposed involving attack of OH- on beta-P2W18O626-, loss of monomeric W(VI) from the M-3 (M3O13) terminal cap, isomerization of the resulting lacunary compound to alpha-P2W17O6110-, and finally reaction of this species with monomeric W(VI) to form the thermodynamic and observed product, alpha-P2W18O626-.