Recently, ongoing chronic liver disease with persistent viraemia has been described in hepatitis B virus (HBV) carriers despite the presence of anti-HBe. This has been attributed to infection with pre-C-region-mutated HBV variants. To investigate the possible existence and the prevalence of HBV variants in Morocco and the correlation between HBV DNA detection by polymerase chain reaction and pre-S1 antigenaemia, we tested twenty blood donors, HBsAg chronic carriers for more than one year. The diagnosis of such HBeAg-negative HBV variants was determined by a previously described rapid detection method using selective oligonucleotide hybridization. Probes M0, M1 and M2 correspond, respectively, to a non-mutated distal pre-C sequence, a one-point-mutated sequence with a TAG stop codon at pre-C codon 28 and a two-point-mutated sequence with codon 28 TAG and codon 29 GAC. All the 5 HBeAg-positive samples hybridized with the M0 wild-type probe only. Among the anti-HBe-positive samples, one hybridized with the M0 probe only, whereas another hybridized with none of the oligoprobes. The 13 remaining HBeAg-negative cases hybridized with the M1, M2 or combined M0, M1 and M2 probes. Seven of the 13 HBeAg-negative samples hybridized with more than one probe. DNA sequencing confirmed mixed distal pre-C sequence changes in samples hybridizing with more than one probe. These data demonstrate the existence, in patients, of HBV variants containing an inactive pre-C region and hence the incapacity to synthesize pre-C-region-derived HBeAg.