Twenty-eight cases of lipoid proteinosis have been identified in a highly inbred White-Khoikhoi ("Hottentot") hybrid community living in Namaqualand, South Africa. The clinical manifestations of the disease are described, and a genetic analysis is presented. Genealogic studies have shown that the autosomal mutant gene for lipoid proteinosis was introduced into South Africa by a German settler and his sister in the mid-17th century. A great-grandson of that settler carried the gene to Namaqualand, where several generations of inbreeding have produced numerous affected homozygotes.