High serum concentrations of lipoprotein (a) [Lp(a)] are considered a risk factor for premature atherosclerosis. Besides apolipoprotein B-100, Lp(a) consists of apolipoprotein (a) [apo(a)], which shows a remarkable size polymorphism. The serum concentration of Lp(a) is considerably influenced by this apo(a) phenotype. Because Lp(a) is synthesized in the liver, we wondered whether and to what extent Lp(a) levels might be affected by acute liver disease. We compared Lp(a) serum concentrations in 74 patients (54% male, 46% female; mean age, 46 years) with acute viral hepatitis (32, 28, and 14 with hepatitis A, B, and C, respectively) with those in 404 healthy controls (57% men, 43% women; mean age, 47 years). In addition, the intraindividual course of Lp(a) concentration during and after acute hepatitis was followed in a subgroup of 23 patients (15, 6, and 2 with hepatitis A, B, and C, respectively). During acute hepatitis, median Lp(a) concentrations in the patient group were significantly diminished compared with controls (7 vs. 17 mg/dL;P < .0001, Mann-Whitney test). Any bias by an unequal isoform distribution was excluded because there was no significant difference in the isoform distribution between patients and controls (P > .10, chi2 test). Furthermore, the decrease in Lp(a) concentration during acute hepatitis was independent of the molecular weight of the apo(a) isoform. Longitudinally observed patients showed a marked increase in Lp(a) concentration during convalescence (7 to 32 mg/dL;P < .0001, Wilcoxon test). Our results show that acute hepatitis is associated with decreased Lp(a) serum levels. Further studies are needed to evaluate whether Lp(a) serum concentration might be clinically useful as a parameter of liver function.