The tetraazamacrocyclic ligand TRITA4- is intermediate in size between the widely studied and medically used 12-membered DOTA4- and the 14-membered TETA4-. The kinetic inertness of GdTRITA- was characterized by the rates of exchange reactions with Zn2+ and Eu3+. In the Zn2+ exchange, a second order [H+] dependence was found for the pseudo-first-order rate constant (k0 = (4.2 ± 0.5) × 10-7 s-1; k′ = (3.5 ± 0.3) × 10-1 M-1S-1, k″ = (1.4 ±0.4) × 103 M-2s-1)- In the Eu3+ exchange, at pH <5 the rate decreases with increasing concentration of the exchanging ion, which can be accounted for by the transitional formation of dinuclear GdTRITAEu2+ species. At physiological pH, the kinetic inertness of GdTRITA- is considerably lower than that of GdDOTA- (t1/2 = 444 h (25°C) vs. 3.8 × 105 h (37°C), respectively). However, GdTRITA - is still kinetically more inert than GdDTPA2-, the most commonly used MRI contrast agent (t1/2 = 127 h). The formation reactions of LnTRITA- complexes (Ln = Ce, Gd and Yb) proceed via the rapid formation of a diprotonated intermediate and its subsequent deprotonation and rearrangement in a slow, OH- catalyzed process. The stability of the LnH2TRITA* intermediates (log KLnH2L* = 3.1-3.9) is lower than that of the DOTA-analogues. The rate constants of the OH- catalyzed step increase with decreasing lanthanide ion size, and are about twice as high as for DOTA-complexes. © The Royal Society of Chemistry 2005.