We report the identification and initial family and population studies of a previously undescribed serum protein polymorphism with two allelic forms. It was discovered in Hutterites, a reproductively isolated religious sect, and is also present in Australian aborigines and a sample of Chicago residents. A two-allele model is consistent with the segregation pattern observed in five kindreds within our initial study group. This polymorphism, provisionally designated SPPM-158, appears as a horizontal (charge-based) doublet in silver-stained ISO-DALT high-resolution two-dimensional electrophoresis gels. It is a low-concentration polypeptide (approximately 1 mg/dL) that has an apparent MWSDS of 43.6 kD and an isoelectric point of approximately 5.5. We infer that it circulates as a multimer or in a high-molecular-weight (greater than 200 kD) complex with other proteins because it is not observed in normal body fluids derived from physiologically ultrafiltered plasma such as amniotic fluid, urine, or cerebrospinal fluid; however, it is present in urine of patients with glomerular proteinuria. The high heterozygosity rates imply utility of this new serum protein marker for both forensic and population studies.