A rational attitude toward serum alanine aminotransferase measurement by blood banks, based on a longitudinal study of a cohort of repeat blood donors. A cohort of 879 blood donors was followed over a 3-year period. Of the 3858 units of blood collected, 112 (2.9%), obtained from 64 donors, had an alanine aminotransferase (ALT) activity over 45 IU per L; of these, 39 had a single ALT elevation. The incidence of ALT increase was 2.01 per 100 units, or 5.1 per 100 donors, per year. The pattern of elevated ALT was followed in 72 donors, 54 of whom were from the 64 cited above. At the second blood donation (BD2), about 5 months later, 62.5 percent had a normal ALT value, and most (91%) retained those values at blood donation 3 (BD3). However, 19 (70.3%) of the 27 whose ALT levels had not returned to normal at BD2 had an increased value at BD3. These results led to the formulation of the following algorithm to improve the management of blood donors; at the first donation, the ALT assay is done after the blood collection, but, at the next donation, the ALT level is measured before donation if the preceding ALT activity had been abnormal. If ALT is elevated, blood is not collected. Three consecutive ALT elevations are a criterion for permanent exclusion of the donor. 