We describe temperature-responsive protein pores containing single elastin-like polypeptide (ELP) loops. The ELP loops were placed within the cavity of the lumen of the alpha-hemolysin (alpha HL) pore, a heptamer of known crystal structure. The cavity is roughly spherical with a molecular surface volume of about 39 500 angstrom(3). In an applied potential, the wild-type alpha HL pore remained open for long periods. In contrast, the ELP loop-containing alpha HL pores exhibited transient current blockades, the nature of which depended on the length and sequence of the inserted loop. Together with similar results obtained with poly(ethylene glycols) covalently attached within the cavity, the data suggest that the transient current blockades are caused by excursions of ELP into the transmembrane ss-barrel domain of the pore. Below its transition temperature, the ELP loop is fully expanded and blocks the pore completely, but reversibly. Above its transition temperature, the ELP is dehydrated and the structure collapses, enabling a substantial flow of ions. Potential applications of temperature-responsive protein pores in medical biotechnology are discussed.