A possible association between intrahepatic cholestasis of pregnancy (ICP) and human-leukocyte histocompatibility (HLA) antigens--used as genetic markers--was studied in 100 women with ICP compared to 100 multiparous women without a past history of the disease. Because we previously found a higher frequency of ICP in women with an overt Araucanian Indian descent than in Chilean Caucasoids, women from both ethnic groups were studied. Among the 37 specificities of the HLA system studied (17 of HLA-A, 16 of HLA-B, and 4 of HLA-C series), only HLA-BW16 showed a tendency to be more frequent in women with ICP rather than in control women. This finding appears to be related with ethnic origin and not ICP, HLA-BW16 was significantly more frequent in women with Araucanian Indian descent (43.4%) than in Chilean Caucasoids (16.3%) (p less than 0.01). The high frequency of HLA-BW16 in the predominantly Caucasoid population in Chile, in comparison with Caucasians in Europe and in North America, may be another indicator of their ethnic admixture with aborigine groups. The high frequency of HLA-BW16 reported in North American Indian-admixed groups (16%) suggests that HLA-BW16 may be a genetic characteristic common to some aboriginal populations in North and South America.