The complete nucleotide sequence of the Nepali strain TK15/92 of hepatitis E (HEV) was determined. It showed the highest sequence homology with the Burmese B1 strain, but closer evolutionary relatedness to the Indian strains. Difficulties in reverse-transcribing and amplifying the hypervariable region in ORF1 suggested that strong secondary structures might be intrinsically responsible for the high mutational rate observed in this region of the HEV genome.