The signficance of the amino acids in positions 29 and 31 of the human calcitonin (HCT) chain were examinedThese positions, in this peptide, are resp. occupied by valine and alanine.A synthetic analog in which these amino acids had been replaced by the corresponding amino acids of salmon calcitonin (SCT 1), i.e. serine and threonine, showed five times greater hypocalcemic activity than natural HCT and a slightly longer duration of action.Reversal of their sequence to Ala29 and Val31, as they occur in two isohormones of SCT 1, yielded a synthetic analog of HCT with very much weaker hypocalcemic potency and its duration of effect was also shorter.The importance of these two positions is discussed by reference to SCT 1 and its isohormones.