The development of rapid, low-cost point-of-care approaches for the quantitative detection of antibodies would drastically impact global health by shortening the delay between sample collection and diagnosis and by improving the penetration of modern diagnostics into the developing world. Unfortunately, however, current methods for the quantitative detection of antibodies, including ELISAs, Western blots, and fluorescence polarization assays, are complex, multiple-step processes that rely on well-trained technicians working in well-equipped laboratories. In response, we describe here a versatile, DNA-based electrochemical "switch" for the rapid, single-step measurement of specific antibodies directly in undiluted whole blood at clinically relevant low-nanomolar concentrations.