Prealbumin (PA) measurements were made by electrophoretic and radial immunodiffusion techniques in three alpha-1-antitrypsin deficient Pi-D) serum samples. The deficiency was characterized as phenotype ZZ (homozygous). In two out of three serums PA was undetectable, as revealed by the absence of radiothyroxine distribution in the PA area, whereas quantitative estimates of PA by radial immunodiffusion showed very low levels (2--7 mg/100 ml) thus corroborating electrophoretic observations; low PA binding of T4 tracer was noted in another Pi-D serum. The total protein and laboratory thyroid function (thyroxine, triiodothyronine, and free thyroxine index concentration) measurements were normal, and the decrease in PA could not be explained on the basis of surgery, protein malnutrition, or cirrhosis. These and other observations described in this preliminary communication have served to raise the possibility of severe prealbumin deficiency being associated with alpha-1-antitrypsin deficiency, while the presence of low-but-not-absent PA in another Pi-D case might also suggest subgroup classification of the phenotype ZZ based on degrees of PA deficiency.