We quantitated α1‐antitrypsin mRNA in normal, α1‐antitrypsin‐deficient cirrhotic and biliary cirrhotic livers using two‐dimensional electrophoretograms of [35S] methionine‐labeled translational products of total hepatic RNA and RNA/DNA hybridization. α1‐antitrypsin precursor product was identified by immunoprecipitation. The relative abundance of α1‐antitrypsin product from normal (0.989 ± 0.197), cirrhotic (0.956 ± 0.062) and α1‐antitrypsin deficient (0.818 ± 0.12) livers was not significantly different. Although (RNA/DNA) was decreased in the PiZZ cirrhotic livers compared to normal (0.56 ± 0.045 vs. 0.95 ± 0.225), it equaled that found in the PiM cirrhotic livers (0.56 ± 0.055). The concentration of α1‐antitrypsin mRNA [relative abundance × (RNA/DNA)], while decreased in PiZZ compared to normal liver, is thus no different in PiZZ cirrhotics than in PiM cirrhotics. We confirmed this observation by quantitation of the α1‐antitrypsin mRNA using an α1‐antitrypsin genomic probe. By RNA/DNA hybridization, α1‐antitrypsin mRNA was equal in PiM cirrhotic and PiZZ cirrhotic (38.48 ± 4.5 vs. 31.93 ± 2.1), but significantly decreased from noncirrhotic PiM liver (58.36 ± 12.7). We conclude that α1‐antitrypsin mRNA is decreased in cirrhosis of any etiology, and this decrease appears to represent a general response of the liver to injury. Since the decreased α1‐antitrypsin mRNA in PiM cirrhotics is associated with normal serum α1‐antitrypsin levels, it is unlikely that the decreased α1‐antitrypsin mRNA in PiZZ cirrhotics accounts for their decreased serum levels.