It is known that interferon-gamma (IFN gamma) is not effective in inducing a sustained inhibition of HBV replication in patients with chronic HBV infection in contrast to interferon-alpha (IFN alpha). To determine whether this was related to IFN gamma receptor (IFN gamma-R) underexpression, binding characteristics of IFN gamma to peripheral blood lymphocytes were studied in chronic HBV infection using radioiodinated recombinant IFN gamma. Peripheral blood lymphocytes from patients with chronic HBV infection (n = 20), normal healthy controls (n = 12) and patients with non-viral related chronic liver disease expressed a similar number of IFN gamma-R (medians (ranges): 1891 (1581-2515); 1916 (1589-2441); 1893 (1692-2104) sites/cell, respectively, p = N.S.) with a similar dissociation constant (Kd approximately 0.7-2.7 nM). There was no correlation between IFN gamma-R expression and serum transaminase, serum HBsAg and HBV-DNA titres and liver histology. IFN alpha therapy in vivo also did not enhance IFN gamma-R expression (n = 3). There is therefore, no evidence from this data that IFN gamma-R is underexpressed in patients with chronic HBV infection to account for the difference in clinical response to these two forms of therapy.