We have used direct DNA inoculation to study the in vivo induction of both humoral and cellular immune responses to hepatitis C virus (HCV) encoded structural antigens. Following immunisation of mice, immune responses were compared using plasmids encoding full-length or partial HCV gene sequences for the nucleocapsid and envelope E2 proteins. Plasmids encoding secreted or non-secreted forms of the immunogens, including constructs expressing HCV sequences fused with the hepatitis B virus surface antigen (HCV-HBV chimeras), were evaluated. Results indicate that: (i) all constructs induced specific anti-HCV antibodies; (ii) antibody titres ranged from 1:100 to > 1:100,000; (iii) all HCV DNA immunogens induced a predominant Th1 response with the induction of IgG2a antibodies; (iv) the secretion level of the antigens and immune responses was not always correlated and (v) CTL could be detected against both HCV and HBV determinants.