The ligand-substitution reaction of M(tpps)(4-) (M = Zn, Cd, Pb; H(2)tpps(4-) = 5, 10, 15, 20-tetrakis(4-sulfonatophenyl)porphyrin) with N,N’-1,2-ethanediylbis[N-(carboxymethyl)glycine] (H(4)edta) and the acid-dissociation reaction of the metalloporphyrins are inhibited by the presence of 18-crown-6 (18C6). The kinetics and mechanism were studied to clarify the effect of 18C6 on the reactions at pH 8-9.5, 25 degrees C, and I = 0.1 M (LiNO3). The rate suppression by 18C6 was explained by the formation of [M(tpps)(18C6)](4-) as a precursor complex. The rate equation for the decrease of M(tpps)4- is expressed as -d[M(tpps)’]/dt = (k(1)[Hedta(3-)] + k(2)K(MPL)[18C6][Hedta(3-)] + k(3)[H+](2) + k(4)K(MPL)[18C6][H+](2))(1+K-MPL[18C6])(-1)[M(tpps)’], where [M(tpps)’] = [M(tpps)(4-)] + [M(tpps)(18C6)], and K-MPL = [M(tpps)(18C6)(4-)][M(tpps)(4-)](-1)[18C6](-1). The values of k(1) (mol(-1) dm(3) s(-1)), k(3) (mol(-2) dm(6) s(-1)), and K-MPL (mol(-1) dm(3)) were found to be 0.00, 10.5 +/- 0.9, and 10(2.5+/-0.1) for Zn(tpps)(4-), 6.4 +/- 0.2, (7.1 +/- 0.3) x 10(12), and 10(2.7+/-0.1) for Cd(tpps)(4-), and 2.9 +/- 0.1, (1.85 +/- 0.05) x 10(12), and 10(1.8+/-0.1) for Pb(tpps)(4-), respectively. The k(2) and k(4) values were not able to be determined for all the metalloporphyrins because k(1) much greater than k(2) and k(3) much greater than k(4). The intermediate, [M(tpps)(18C6)](4-), hinders the attack of Hedta(3-) or H+. The intermediate is formed by the interaction of the metalloporphyrin plane with 18C6 ring, and the interaction was confirmed by H-1 NMR and absorption spectra. The H-1 NMR signal of 18C6 shifted to a higher field and the change in absorption spectra was larger for Cd(tpps)4- than for Zn- and Pb(tpps)4-. The detailed reaction mechanism and the formation of the intermediates are discussed.