Quantitative characterization and alpha 1-antitrypsin (alpha 1AT) Pi phenotyping by isoelectric focusing (IEF) and immunofixation electrophoresis (IFE) were done on 84 patients with trisomy 21, divided into two groups, and on their parents. Group A consisted of 42 subjects whose parents were less than 30 years at the time of the patient's birth; group B, of 42 subjects whose parents were more than 35 years. The results were compared with those found in a group of normal subjects. Statistical analysis of the Pi phenotype distribution and the frequency of variant phenotypes does not support a causal relationship between the Pi phenotype and the chromosomal errors responsible for Down syndrome.