Hemolysates of erythrocytes from more than a quarter million people in Alabama, USA, were electrophoresed on cellulose acetate, pH 8.4, and those samples exhibiting an abnormality were electrophoresed in citate agar, pH 6.0. The globin chains of mutants other than Hb S and C were electrophoresed in urea-mercaptoethanol buffers at pH 8.9 and pH 6.0, and 60 of them were analyzed structurally. Of about 6000 samples from whites, only 3 contained abnormal Hb.sbd.Hb D Los Angeles, Hb J Baltimore, and one unidentified. Of 249,000 samples from blacks, about 29,000 contained electrophoretically detectable abnormalities, most of them associated with Hb S or C, present in a frequency of about 9% and 3%, respectively. About 1000 samples resolved into patterns of potential clinical significance. Twenty other mutant Hb were detected, in various genetic combinations in 164 kindreds; 4 of these.sbd.Hb Alabama, Montgomery, Titusville and Mobile.sbd.were previously unknown. The methods used are rapid, economical and well suited for large scale surveys. They provide highly specific characterizations of many mutant Hb, and no discrepancies were found between the presumptive identifications based on these characterizations and the definitive identifications obtained from structural analyses.