Small oligomers of amyloid beta (A beta) are suspected to be the key to Alzheimers disease (AD). However, identifying these toxic species in the background of other similar but nontoxic A beta aggregates has remained a challenge. Recent studies indicate that A beta undergoes a global structural transition in an early step of aggregation. This transition is marked by a strong increase in its affinity for cell membranes, which suggests that the resultant oligomers could be the key to A beta toxicity. Here we use this increased membrane affinity to develop a rapid, quantitative, cell-free assay for these bioactive oligomers. It uses fluorescence correlation spectroscopy of fluorescently labeled A beta and requires only 30 s of measurement time. We also describe a simpler (though less rapid) assay based on the same principles, which uses a dialysis step followed by conventional fluorescence spectroscopy. Our results potentially provide a much-needed high-throughput assay for AD drug development.