Class III gene rearrangements have been examined in Thai/Chinese individuals with supratypes bearing defective or null C4 alleles. Genomic DNA from C4 null supratypes was probed with an almost full-length 21-OH probe following digestion with Taq I and Kpn I. The HLA-B17 C4A3 BQ0 BfS DR3 Thai/Chinese supratypes (which may be associated with insulin-dependent diabetes mellitus in Orientals) lacks a 3.2 kb Taq I and a 3.9 kb Kpn I fragment hybridizing with the 21-OH probe. Similar gene rearrangements are found in Caucasoid diabetogenic supratypes HLA-B18 C4A3 BQ0 BfF1 DR3 and HLA-B8 C4AQ0 B1 BfS DR3. Interethnic comparisons suggest that class II and class III interactions may be important in disease susceptibility. By contrast, neither of two Thai/Chinese supratypes with C4AQ0 appear to have major class III gene rearrangements; disease association studies will determine the significance of C4 deficiency per se. As in Caucasoids, the electrophoretically fast C4 allele, C4A6, in Orientals has been shown to correlate with a 12 kb Bgl II fragment hybridizing with a C4 probe. It is likely that the HLA-B17 C4A6 B1 BfS DR7 supratype marks a highly conserved MHC chromosomal segment.