Among 200,000 infants screened for alpha 1-antitrypsin (alpha 1-AT) deficiency, 125 Pi Z, 48 Pi Z, 1Pi S-, and 2 Pi Z- children were followed up prospectively. Eleven percent of the Pi Z infants had neonatal cholestasis, and at 2 years of age three of them had cirrhosis. About 50% of the asymptomatic Pi Z and Pi Z- subjects occasionally had serum alanine aminotransferase (ALAT) levels above normal, and in 15% of them the levels were probably permanently increased during the first two years of life. Two previously healthy Pi Z children had transient symptoms of liver disease at age 2 years in connection with severe infections. The Pi SZ children had no significant clinical liver disease and only two had abnormal serum ALAT levels. Among Pi Z children up to 2 years of age the following diseases were also encountered: eight had recurrent bronchitis with wheezing, two had persistant cough (both had cirrhosis), one had severe pneumonia, one was mentally retarded, three had urinary tract infections, six had pronounced eczema, one had allergic shock, and three had congenital malformations. Among the Pi SZ children one had recurrent bronchitis, one had eczema, and one had juvenile rheumatoid arthritis. Three children, two Pi Z and one Pi SZ, have died. The Pi Z- and Pi S- subjects were healthy. In conclusion a variety of significant symptoms were observed in about 30% of the Pi Z children compared with 6% of the Pi SZ children during the first two years of life.