African trypanosomes periodically change the antigenic character of their cell surface by replacement of their surface coat which is composed of variant surface glycoprotein (VSG). This is accomplished by alternate expression of one of about 200 VSG genes in the repertoire and regulated at the level of transcription. The molecular mechanisms which mediate this process are unknown. However, VSG gene sequences rearrange and this rearrangement may be associated with regulation of VSG gene expression. Expressed and VSG gene sequences and their flanking sequences will be isolated by molecular cloning. Unique and common regions among sequences from different variant antigenic types (VATs) and different isolates of the same VAT will be identified, characterized and localized in the VSG gene coding and flanking regions. The behavior of the characterized sequences during antigenic variation, transformation to procyclic forms which express no VSGs, and after completion of the life cycle through the insect vector will be determined. These experiments will test critical elements of hypotheses proposed to provide the molecular basis for antigenic variation. They are designed to generate data for the formulation of alternative models, if necessary.