Stochastic sensing of single molecules passing through ion channels is becoming an established technology for detecting minute quantities of analytes in solution; however, until now this approach has been limited to detection of molecules small enough to pass through the channel. In this issue, Bayley and colleagues present a new type of biosensor that can detect even macromolecules in nanomolar concentrations. Within the pore of an α-hemolysin channel, they tethered a polyethylene glycol chain with a biotinyl group attached to its free end. When the modified channel was incorporated into a lipid bilayer, the biotinyl group was free to move from one side of the membrane to the other, where it could be captured by streptavidin. Capture was detected by changes in ionic current through the channel. The method can potentially provide both quantification and identification of a protein analyte at the single-molecule level (see pp. 1037 and 1091).