Patients undergoing long-term hemodialysis are at high risk of acquiring hepatitis B yet tend to have poor rates of response to hepatitis B vaccine. The effect of recombinant human γ-interferon (2 million units/m2) on the response to a recombinant hepatitis B vaccine was evaluated in a prospective, randomized controlled trial in 81 hemodialysis patients. A similar proportion of both groups of vaccinees ultimately developed antibody to HBsAg including 81% of the 41 recipients of vaccine alone (group I) and 89% of the 40 recipients of vaccine with γ-interferon (group II). However, the antibody to HBsAg response occurred earlier in recipients of vaccine with γ-interferon, so that at 4 mo 63% of group I and 88% of group II had antibody to HBsAg (p < 0.025). Furthermore, titers of antibody to HBsAg tended to be higher in the vaccinees given interferon; the final geometric mean titers were 232 IU/L in group I and 330 IU/L in group II (p = not significant). Retrospective testing for antibody to hepatitis C virus revealed that 21 (26%) hemodialysis patients were seropositive at entry into this trial, but the presence of antibody to hepatitis C virus did not appear to affect the response rate to the hepatitis B vaccine. These results suggest that the effects of γ-interferon as an adjuvant in increasing the response rate to hepatitis B vaccination deserve further evaluation perhaps most appropriately in persons who have not responded to an initial course of vaccine. (HEPATOLOGY 1990;12:661–663).