The serum level of alpha-fetoprotein in normal adults is lower than 10 ng/ml. High levels of alpha-fetoprotein in adults are linked to cirrhosis, acute or chronic hepatitis, hepatocellular carcinomas and other pathologies, as well as to foetal malformation, and this protein is therefore used as a regular clinical marker for these diseases. We report a Spanish family in which very high levels of alpha-fetoprotein have been detected in nine members from the screening of a total of 17 relatives. These levels of alpha-fetoprotein are not accompanied by a causing pathology, are inherited as an autosomal dominant genetic trait, and are associated to a G-->A substitution at position -116 of the 5'-flanking region of the alpha-fetoprotein gene. This is an unusual benign trait of hereditary persistence of alpha-fetoprotein. This paper provides a detailed clinical report of the family including a study of the molecular basis of this trait. The desirability of a test to detect and/or rule out this benign trait in adults with abnormal levels of alpha-fetoprotein is considered.