In clinical research, the definition of the upper limit of normal (ULN) alanine transaminase (ALT) is never detailed. However, such a definition can vary and may have practical consequences. Our aim was to assess factors associated with serum ALT activity in apparently healthy subjects and then to apply seven different definitions of ULN in three different populations so as to assess the prevalence of subjects with normal ALT among blood donors and among hepatitis C patients before (normal ALT hepatitis C patients) and after treatment ( Measuring serum alanine transaminase (ALT) activity is a very common screening test as part of a routine evaluation of patients. The definition of normal and abnormal serum ALT activity has pragmatic consequences in at least three circumstances. The first involves the selection of donors so as to prevent the transmission of non-A, non-E viruses. The second is the identification, among patients with chronic hepatitis C, of a subgroup of patients with chronic hepatitis C and normal ALT who could represent a specific group in terms of liver fibrosis progression 1 or efficacy of interferon (IFN) treatment. 2 The third concerns the definition of a response after treatment of hepatitis C in which serum ALT measurements are very often used to define responders. 3 In these three circumstances, a change in the definition of the normal value or in the prevalence of factors associated with ALT serum activity could cause practical changes. For example, a decrease in the upper limit of normal (ULN) value reduces the number of donors in a blood bank, decreases the prevalence of patients with chronic hepatitis C and normal ALT, and decreases the number of IFN responders in a randomized trial.To better understand the definition of normal and abnormal ALT, we assessed, in a prospective cohort of 1,033 blood donors, the distribution and factors associated with abnormal ALT. From these results, a new definition of the ULN ALT was suggested. Then, to observe clinical implications, we applied seven different definitions of an upper normal limit to three populations of subjects with normal ALT: blood donors, hepatitis C patients before treatment (normal ALT hepatitis C patients), and after treatment (IFN responders). All ALT measurements were performed using the same technique. PATIENTS AND METHODSBlood Donors. A total of 1,085 donors were consecutively investigated in the Blood Center of Hô pital Broussais in Paris, France. From this population, 52 donors were excluded because of presence Abbreviations: ALT, alanine transaminase; IFN, interferon; ULN, upper limit of normal; GGT, ␥-glutamyl transpeptidase; BMI, body mass index.*The MULTIVIRC group (Groupe Hospitalier Pitié-Salpêtrière): Service d'Hépato-Gastroentérologie: