Using the method of radioisotopic exchange, the substitution of zinc (II) ion in zinc-EDTA complex was observed to occur at a measurable rate over a concentration range of 10 −5–10 −6 M in both species and within the pH range of 6–7 at room temperature. Because of erratic behaviour of 65Zn ion at very low tracer concentrations (∼10 −12 M) suggestive of radiocolloid formation, exchange experiments were done using freshly prepared 65Zn-labelled chelate. The substitution rate of zinc (II) ion in zinc-EDTA at 20°C in 0·05 M acetate buffer was summarized within experimental error by: R = k 1[Zn 2+][ZnEDTA 2−] + k 2[ZnEDTA 2−][H +] + k 3[ZnEDTA 2−][H +] 2 + k 4[ZnEDTA 2−] where R is the substitution rate in units of mole/l. per sec and the specific rate constants have the values at 20, 30 and 40°C; k 1 = 4·13, 26 and 96 1/mole per sec; k 2 = 76, 178 and 256 l/mole per sec; k 3 = (1·3, 0·68 and 1·5) × 10 8 l 2/mole 2 per sec; and k 4 = (7·7, 15, 17) × 10 −5 sec −1, respectively. Activation energies corresponding to these values are: 29· 2, 12· 5, 1·6 and 7·7 kcal/mole, respectively. The zinc-EDTA chelate was quite labile and substitution of zinc (II) ion through the spontaneous decomposition of chelate was an appreciable contribution to the overall reaction rate in all experiments. The reaction mechanism postulated indicated several parallel paths involving the unprotonated zinc-EDTA chelate and also the protonated species: ZnHEDTA − and ZnH 2EDTA°, suggesting that acid-catalysed decomposition of the chelate facilitated the disruption of metal-chelate bonds in the transition state. Comparison of these results with similar studies of other transition element EDTA chelates indicate that zinc (II) chelate undergoes substitution more rapidly than the d 7 and d 8 cobalt and nickel chelates. This finding is qualitatively in agreement with crystal field predictions assuming octahedral configuration and a weak field metal-EDTA interaction.