Two atypical serological markers of hepatitis B virus (HBV) infection were detected in 19 patients during a 18-month period study. Pattern 1 (10 patients) was consistent with HBV-2 infection. Reactivity of HbsAG was confirmed by neutralization tests; the absence of other markers was also verified, included anti-HBcIgM. Three of the patients were classified in high risk groups and seven in the low risk groups for hepatitis B; in none of them was co-infection with hepatitis A virus (HAV) detected. Pattern 2 (9 patients) was characterized by the detection of HBsAg and HBeAg and the absence of other hepatitis B markers. Six of these patients were HIV-positive patients and had increased and persistent levels (for longer than 12 weeks) of these markers. In the three remaining patients (with no underlying immunological disorders) there was a loss of these markers within a variable time (2 days to 16 weeks). Nevertheless, DNA-VHB was detected in one of these serum samples once all markers of virus B had disappeared.