With respect to T----R-structural transformation, cobalt insulin hexamers appear as dimers of two positively cooperative trimers which are related by negative cooperativity. Transformation of the first trimer causes polarization of the hexamer which is insurmountable by inorganic anions (SCN theta) used as transforming agents, and in the case of phenolic agents (m-cresol), which can achieve complete transformation of the hexamer, allows the identification of the T3R3 intermediate. Zinc insulin hexamers are also transformed in a stepwise manner, but for the first step the sigmoidal shape of the titration curve cannot be detected.