Following acute hepatitis B virus (HBV) infection, most individuals develop antibodies to HBV surface (anti-HBs) and core antigen (anti-HBc). Prevalence studies have shown that 10-18% develop anti-HBc in the absence of detectable anti-HBs. We report four such cases, all with persistence of serum anti-HBc, who had evidence of a second period of active HBV replication as demonstrated by the reappearance of serum hepatitis B surface antigen (HBsAg). In one patient, an HBsAg subtype difference indicated that the second period of HBsAg-positivity was due to a reinfection. In the other cases, reactivation may also explain the findings. All cases were anti-HIV-1 seropositive at the time of reappearance of HBsAg. There is experimental evidence that anti-HBc has a protective effect against HBV infection; however, this may require intact cell-mediated immunity to be effective. HIV-1 infection may render such patients susceptible to reinfection. Alternatively, some patients with anti-HBc, but without detectable anti-HBs may have latent HBV infection. Immunosuppression associated with HIV-1 infection may allow reactivation.