People living in areas endemic for Plasmodium falciparum develop humoral responses which may contribute to protection against clinical disease but the specificity of such protective antibody responses remains to be defined. Antibodies disrupting erythrocyte rosettes have been associated with protection against cerebral malaria, and antibodies agglutinating infected erythrocytes with reduced episodes of clinical disease. We have studied the capacity of serum from Papua New Guinean adults and children with a spectrum of malaria exposure, including children and adults at the time of clinical disease, to disrupt erythrocyte rosettes and cause agglutination of infected erythrocytes. Using a single parasite isolate, almost all sera from adults from highly endemic areas agglutinated infected erythrocytes, and the majority disrupted rosettes, in some cases at greater titres than hitherto described. There was a correlation between rosette disruption and agglutination in highly exposed adults. Rosette disrupting antibodies were equally frequent in children with cerebral and uncomplicated malaria. Antibodies causing rosette disruption were frequent only in adults with a long history of malarial exposure. Rosette disrupting antibodies do not appear to protect Papua New Guinean children or adults against cerebral malaria.