The level of serum-soluble interleukin-2 receptor (sIL-2R) was measured in 32 patients to investigate the effect of prednisone and alpha-interferon therapy on chronic hepatitis B virus infection. All the patients were seropositive for hepatitis B surface antigen and hepatitis B e antigen, with histological evidence of chronic persistent or chronic active hepatitis. Twenty-six patients received oral prednisone, followed by subcutaneous recombinant alpha-interferon, and six patients received multivitamin tablets and served as controls. After 4 wk of prednisone in reducing dosage, serum sIL-2R fell significantly from 673.6 +/- 52.9 U/ml to 584.8 +/- 39.4 U/ml (mean +/- SE, p less than 0.05). It rose to 733.4 +/- 45.7 U/ml (p less than 0.05) on the 4th wk of interferon, but returned to pretreatment level at completion of interferon. There was a significant correlation between serum sIL-2R and alanine aminotransferase levels (r = 0.36, p less than 0.001). The level of serum sIL-2R before treatment and its response to prednisone and interferon were not useful in predicting seroconversion of hepatitis B e antigen and anti-hepatitis B e.