Twenty‐one pretreatment variables were assessed for their significance in response prediction using data from 114 patients given α‐interferon for chronic hepatitis B virus infection. In those patients who had received a minimum of 90 million units per m2 total dose over 12 weeks, a negative anti‐human immunodeficiency virus antibody status (p < 0.001), chronic active hepatitis on liver biopsy (p < 0.005), high AST level (p < 0.001), low hepatitis B virus DNA level (p < 0.001) and a history of acute hepatitis (p < 0.005) were all associated with an increased likelihood of response on univariate analysis. On stepwise logistic regression analysis, hepatitis B virus DNA, AST and a history of acute hepatitis predicted response independently (p < 0.05). The most reliable combination of predictive factors was a negative anti‐human immunodeficiency virus antibody status, with either a positive history of acute icteric hepatitis and AST > 45 IU per liter or no history of acute icteric hepatitis and AST > 85 IU per liter, which predicted response in 77% with a specificity of 79% (p < 0.001). The loss of HBsAg in addition to HBeAg and hepatitis B virus DNA was more likely to occur in patients with chronic infection of <2 years duration (p < 0.001).