Recent investigations have established that the genes which encode the classical HLA-A,-B and -c heavy chains are members of a large multigene family of highly related sequences. The functions of the extra genes are unknown but some at least appear to be pseudogenes. Although many of the class I genes appear to map telomeric to the A locus, molecular mapping of the class I chromosomal region is still fragmentary. The complete nucleotide sequences of several allelic genes at the A and B loci and one C locus gene have been established. Sequence comparisons suggest a non-random pattern of substitution and the occurrence of a mechanism analogous to gene conversion which can promote polymorphism by exchange of small stretches of nucleotide sequence between genes. RFLP studies can complement serologically based investigation of class I involvement in disease associations and transplantation studies.