A serial prospective study of cell-mediated immunity to rabbit liver-specific lipoprotein (RLSP) has been done in 26 patients with acute viral hepatitis (AH) (18 HBsAg+ and eight HBsAg-) using a lymphocyte transformation test. An increased stimulation index was recorded in 56% of HBsAg+ cases and in 63% of the HBsAg- group at the first determination within 2 weeks of presentation. A progressive return to normal values was observed during the course of the disease. In one patient, however, the stimulation index remained high at 6 months after presentation and liver biopsy showed the appearance of chronic active hepatitis. Results within the normal range of values were observed when a macromolecular kidney protein fraction was used as antigen: further evidence of an organ-specific component in RLSP preparation to which the immune response seems to be directed. These findings demonstrate the existence of a common and time-limited sensitization to RLSP in acute viral hepatitis irrespective of HBsAg status. It is suggested that RLSP may be a useful alternative to human LSP in evaluating immune reactions in liver diseases.