The human Lewis gene encodes an α(1l,3/1,4)-fucosyltransferase responsible for synthesis of the Lea and Leb antigens. To define the molecular background for non-functional Lewis genes we have sequenced PCR-amplified DNA fragments from two Le(a-b-) individuals. One was homozygously mutated at nucleotides 202 (T→C)and 314 (C→T), altering Trp^68 to Arg and Thr^105 to Met, and the other was homozygously mutated at nucleotides 59 (T→G) and 1067 (T→A), altering Leu20 to Arg and lie356 to Lys. Using PCR we screened for these and additionally one other mutation at nucleotide 508 (G→A) among 40 Caucasians. Of 15 Le(a-b-) individuals, 7 typed as le^59;1067 le^202;314, 4 as le^202;314 and 1 as le^59;1067 le^59;1067. Of 21 Le(a-b+) and 4 Le(a+b-), 17 typed as LeLe and 7 as Lele^202;314. A pedigree study of 8 Lewis-positive individuals showed that the mu- tarions at nucleotides 202 and 314 were located on the same allele.