Current opinion supports the view that immunity to the surface of the trophozoite-infected erythrocyte (IE) is to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP-1). Here we provide further evidence using the mutant cell line 1776/C10 which no longer expresses PfEMP-1 at the IE surface, due to a subtelomeric deletion in chromosome 9. We have measured antibody reactivity to this mutant in comparison to it's intact isogenic parent line 1776, which does express PfEMP-1, using the sensitive technique of flow cytometry. IgG-specific antibodies (subclass IgG1) in the plasma of hyperimmune adults, reacted to 1776 but never to the 1776/C10 mutant. Antibody subclasses were also measured in individual plasma samples to the surface of trophozoite-IE. Predominantly IgG1 antibodies were detected, with a few individual plasma having additional IgG3 antibodies. Previous studies have used the agglutination assay to measure sero-conversion to PfEMP-1. Here we show that both agglutination and flow cytometric methods are comparable, suggesting that agglutination of trophozoite-IE is mediated by IgG antibodies. Comparison of the isogenic cell lines 1776 and 1776/C10 differing in expression of PfEMP-1 provides further evidence that IgG antibodies, in particular of the cytophilic subclasses, mediate recognition of PfEMP-1.