We report clinical and genetic characteristics of seven juvenile hemochromatosis (JH) patients (six females, one male) in two unrelated kinships from the southeastern U.S. All had severe iron overload. Mean age at diagnosis was 20 +/- 5 years (range 8-23 years). In six patients, the mean age at onset of signs and symptoms attributable to iron overload was 15 +/- 2 years (12-18 years); an 8-year-old girl had no symptoms. Six of the seven patients had hypogonadotrophic hypogonadism, two had severe cardiomyopathy, seven had hepatomegaly, two had hepatic cirrhosis, and five had hyperpigmentation. Two of four siblings with JH also had Hashimoto thyroiditis. One patient with severe cardiomyopathy improved with therapeutic phlebotomy, medical therapy for congestive heart failure, and a permanent pacemaker; the other died before phlebotomy was initiated. Estimates of average daily iron absorption before phlebotomy-induced iron depletion were 2.3, 3.1, and 1.7 mg in a male and two females, respectively. Both parents of four siblings with JH were heterozygous at two Ch1q loci (D1S1156, D1S2344); each of the four affected siblings was homozygous at both loci. An unaffected sib was heterozygous at D1S1156. One patient was heterozygous for HFE H63D, five others did not have HFE C282Y or H63D, and one was unavailable for testing. We conclude that JH occurs in the southeastern U.S. It is likely that JH allele(s) in at least one of the present kinships occur(s) on Ch1q, and presumably this represents a mutation(s) of the same gene localized to Ch1q in Italian and Greek JH kindreds. The present cases do not have HFE genotypes typical of hemochromatosis diagnosed in adults. Hashimoto thyroiditis, linked to Ch6p in many kinships, did not segregate with JH alleles on Ch1q in the present kinship.