The immunogenicity and reactogenicity of two influenza vaccines were evaluated in a randomised, double-blind trial in north-east Italy during winter 2005-2006. Of 238 adult subjects (18-60 years of age) with underlying chronic diseases, 120 received MF59-adjuvanted subunit vaccine (Sub/MF59) and 118 received conventional subunit vaccine (Subunit). At 4 weeks post-vaccination, geometric mean titres (GMT) were significantly (P<0.001) increased for both groups. For the A/H3N2 and B strains, significantly (P<0.02) higher GMT were reported for the Sub/MF59 group. The mean-fold increase in titre, the percentage of subjects with at least a four-fold titre increase and the seroprotection rate (>or=1:40) were also higher in the Sub/MF59 group, with the seroprotection rate and four-fold titre increase achieving significance (P=0.002 and P=0.02, respectively) for the A/H3N2 strain. Our results suggest that adults affected by chronic diseases can mount a satisfactory immune response to influenza vaccines, and that these vaccines are well tolerated. Addition of the MF59-adjuvant, however, enhances the immunogenicity of subunit influenza vaccine, conferring superior protection than a conventional subunit vaccine in this population, who are at high-risk of influenza-related complications.