We have analyzed the immunomodulatory effect of 5 and 2 MU of recombinant interferon-gamma (rIFN-gamma) administered to 8 carriers of HBsAg with histologically proven chronic active liver disease. After the rIFN-gamma administration, T8 lymphocyte subsets showed a significant decrease (basal vs. 4 weeks, p less than 0.05) and T4/T8 ratios were higher than the basal values in 6/8 patients. Serum levels of the HLA class I-associated beta 2-microglobulin increased significantly in all patients within the first week of treatment, both with the high (p less than 0.01) and the low (p less than 0.05) rIFN-gamma dose. Then, differences between the two doses reached statistical significance (p less than 0.03). Similar results (p less than 0.05) were obtained by measuring the 2',5'-oligoadenylate (2-5A) synthetase activity, co-occurring with the decreases in HBV-DNA polymerase and HBV-DNA, although no differences were found between the two doses. In addition, levels of 2-5A synthetase correlated significantly with those of beta 2-microglobulin (r = 0.743, p less than 0.01). On the other hand, after the rIFN-gamma administration, all the patients had liver membrane antibodies (LMA) in their serum (p less than 0.05); only two patients (who were anti-HD positive) showed LMA at the end of the follow-up. rIFN-gamma has both antiviral and immunomodulatory effects in HBeAg carriers with chronic liver disease.