Isolates of Plasmodium falciparum commonly undergo a large subtelomeric deletion of the right end of chromosome 9 during in vitro cultivation, accompanied by loss of ability to cytoadhere to melanoma cells and greatly lowered gametocyte production. ItG2, an isolate in which cytoadherence is stable, has undergone a subtelomeric deletion of intermediate length on chromosome 9. We show here that the deletions in all non-cytoadherent clones examined have breakpoints within or delete a novel open reading frame (the breakpoint open reading frame, BPORF) that is a unique sequence in the genome. Surprisingly, in ItG2 BPORF has been removed by an additional 15 kb internal deletion in chromosome 9. These results suggest mechanisms to account for the observed frequent deletion of the right arm of chromosome 9 and for the known stability of cytoadherence in ItG2. However, we were unable to detect var genes in this region of the ItG2 genome. We conclude that the product of a novel gene distinct from the var family is implicated in cytoadherence.