Twenty-four members (4 generations) of a family with alpha 1 antitrypsin deficiency were studied in an attempt to determine the chromosomal location of the Pi system locus. Three alpha 1 antitrypsin alleles (PiM, PiI, and PiZ) and five phenotypes (MM, MZ, MI, IZ, and ZZ) were detected in family members. The quinacrine fluorescent banding technique was successfully utilized to reveal eight polymorphic chromosomal markers in family members. Eight red cell antigens and HL-A antigens were identified for each family member. No linkage between the Pi system and chromosomal markers, four polymorphic red cell antigens, and HL-A antigens was detected. On the basis of this family study, the Pi locus as defined by alpha 1 antitrypsin deficiency does not appear to be on chromosomes 2, 3, 13, 14, 21, or 22 within measurable distance of the markers used.