Giardia lamblia, an intestinal dwelling protozoan parasite, undergoes surface antigenic variation where only one of an estimated 150 variant-specific surface proteins (VSPs) is expressed and present on the surface at any one time. Transcriptional switching between VSPs results in replacement of one VSP by another. The mechanisms that control antigenic variation are poorly understood and difficult to study because there are multiple copies of each VSP and strong similarity with other VSPs. In order to study transcriptional regulation of one specific vsp, a haemagglutinin (HA) epitope-tagged h7 was integrated into the G. lamblia GS genome. We show that HA-tagged H7 undergoes antigenic variation in the same manner as native H7, also present in the GS genome. Control of expression of both HA-tagged H7 and native H7 is independent of each other even though the genes and their surrounding 5' and 3' flanking sequences are virtually identical. Analysis of expressing and non-expressing clones revealed an absence of HA-tagged h7 gene rearrangements upon switching and acetylation of histone lysine residues within the 167 nucleotides 5' to the expressed HA-tagged h7 gene. Lack of vsp rearrangements and acetylation of expressed immediate upstream regions implicates involvement of epigenetic mechanisms in antigenic variation.