Hemoglobin South Florida is a recently identified hemoglobin variant that is not associated with any clinical disorder. The standard electrophoretic procedures routinely utilized to identify hemoglobin variants did not recognize hemoglobin South Florida. The acetylated form of this hemoglobin co-eluted with hemoglobin A1c on a Bio-Rex 70 column. The quantity of this hemoglobin component was consistent with the amount of hemoglobin A1c associated with uncontrolled diabetes mellitus. The affected individuals did not have diabetes. This observation led to the characterization of a hemoglobin variant that otherwise would have gone unrecognized. This is an example of a variant peptide that was unrecognized for two generations in one family. It is likely that this type of unrecognized peptide variation is common in mammals. These silent structural alterations may be responsible for the variable physical responses occurring in humans exposed to the same environmental agents.