Leukocyte immunoglobulin-like receptors (LILRs) resemble killer cell immunoglobulin-like receptors (KIR) in structure and function and the KIR and LILR gene families form the major part of the leukocyte receptor cluster (LRC) of human chromosome 19q13.4. Unlike KIR, the LILR gene clusters do not vary in gene number. However, some individuals lack expression of LILRA3. This null allele has a 6.7-kb deletion, which encompasses the first six translated exons. This haplotype enabled unambiguous direct sequencing of LILRA3 alleles using genomic DNA from individuals heterozygous for the deletion. We have performed nucleotide sequencing of a 2.5-kb region within LILRA3 and identified eight bi-allelic substitutions, four of which were non-synonymous. Two from four previously identified LILRA3 cDNA sequences were confirmed and a further six alleles characterised, of which four will encode unique peptides. At least one of the polymorphic positions identified (encoding residue 84 of the first Ig domain) is likely to directly influence ligand binding. A PCR-SSP molecular genotyping system was developed and used to describe a panel of 172 Caucasoid individuals from South-East England. Six alleles were present in this group but they were unevenly distributed, as three alleles accounted for 88% of the studied chromosomes.