Microcalorimetry measures minute heat changes associated with intra- and intermolecular interactions. It provides a rapid, direct method for determining drug or ligand-target binding affinities, without the need for radiolabelling, immobilisation, or indirect spectroscopic methods. The VP-ITC system is an ultrasensitive isothermal titration calorimeter that uses a cell feedback network (CFB) to differentially measure and compensate for heat produced or absorbed between the sample and reference cell. A major advantage of the VP-ITC system is three users-selectable modes of operation: high gain, low gain and passive. The high gain mode is suggested for most ITC experiments, allowing the fastest re-equilibration between injections, thereby providing the shortest experimental times. The passive mode has the lowest noise, and is useful when examining very small signal changes in systems having slow transients.