The leukocyte immunoglobulin–like receptor (LILR)B3andLILRA6genes encode homologous myeloid inhibitory and activating orphan receptors, respectively. Both genes exhibit a strikingly high level of polymorphism at the amino acid level andLILRA6(but notLILRB3) displays copy number variation (CNV). Although multiple alleles have been reported for both genes, limited data is available on frequencies of these alleles among humans. We have sequencedLILRB3/A6exons encoding signal peptides and ectodomains in 91 healthy blood donors of European descent who carry one or two copies ofLILRA6per diploid genome.Analysis of haplotypes among individuals with twoLILRA6copies, representing the majority in this cohort (N= 86), shows that commonLILRB3andLILRA6alleles encode some distinct amino acid sequences in homologous regions of the receptors, which could potentially impact their respective functions differentially. Comparison of sequences in individuals with one vs. two copies ofLILRA6supports non-allelic homologous recombination betweenLILRB3andLILRA6as a mechanism for generatingLILRA6CNV andLILRB3diversity. These data characterizeLILRB3/LILRA6genetic variation in more detail than previously described and underscore the need to determine their ligands.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00251-022-01286-1.