Apolipoprotein H (APOH), also known as beta2-glycoprotein I, is a major antigen for the production of antiphospholipid antibodies in autoimmune diseases. Previously we have examined DNA variation in the coding region of the APOH gene and determined the molecular basis of the common protein polymorphism. Here we report the results of DNA sequence variation in the entire APOH gene encompassing a 20.3 kb region in 46 Caucasian Americans and 48 African American chromosomes. A total of 150 single nucleotide polymorphisms (SNPs) and one tri-allelic polymorphism were identified, including 8 in the coding region, 14 in the 5'-region and 2 in the 3'- region; the remainder were observed in introns. The observed number of SNPs was higher in the African American sample than in the Caucasian sample (130 vs. 84). We examined the race-specific linkage disequilibrium pattern among SNPs and identified maximally informative SNPs for future association studies. Altogether, we have identified 17 informative SNPs among Caucasians and 35 in blacks. The discovery of a full range of sequence variation and identification of race-specific informative SNPs in the APOH gene may facilitate the rapid evaluation of this variation in relation to autoimmune diseases.