PURPOSE: We assessed the effectiveness of educational interventions for conveying clinical findings and information about hereditary hemochromatosis (HH) and iron overload (IO) to individuals evaluated clinically after initial screening for HH/IO with serum ferritin (SF) concentration, transferrin saturation (TS), and HFE genotyping. METHODS: A questionnaire mailed to 2300 cases and controls 1 month after a letter summarizing clinical findings measured understanding of results and recommendations, knowledge of HH/IO, and satisfaction with information received. RESULTS: Of 1622 (70.5%) participants completing relevant items, 83.6% were satisfied with receiving initial screening results by mail, 93.4% found information clear and easy to understand, 89.2% generally felt they got enough information, but 47.5% still had questions. C282Y/C282Y homozygosity with normal TS/SF predicted the best understanding of genetic results. Many with no mutations thought relatives were at risk. Iron levels created most confusion, and a third incorrectly recalled treatment recommendations. Having any abnormal result, lower education, older age, and being non-white, and/or non-English speaking predicted lower understanding. CONCLUSIONS: Combining genotypic and phenotypic screening for HH/IO creates additional difficulties in communicating results-particularly to those with low health literacy. Explaining aberrant iron TS and SF levels and low-risk genotypes, follow-up recommendations, and risk to relatives will need creative, culturally appropriate strategies. ©2007The American College of Medical Genetics.