Miscellaneous metal cations and EDTA have been used as activators and inhibitors of esterase activity in the thyroid of the guinea-pig. The results indicate that the 5-bromoiondoxyl acetate esterase in the epithelial cells probably consists of two different A-esterase isoenzymes, one present in group I cells (the para-, intra-, and inter-follicular cells) and the other in group II cells (the follicular cells proper). The first isoenzyme seems to be calcium-dependent whereas the other is activated by various metal ions. Ca2+ + Mn2+ and Ca2+ + Co2+ were found to activate the esterase activity in group I cells. EDTA and Mn2+, on the other hand, activated the esterase activity in group II cells.