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A detailed description of a differential isothermal titration microcalorimeter with Peltier compensation is reported here. It can be considered as a heat flux or conduction microcalorimeter with dynamic power compensation. The design, based on the twin principle, is very simple and the manufacture is of low cost and complexity. The system operation is completely automatized and computer controlled, including the data acquisition tasks, the controller of the power compensation feedback loop and the reagent injection system. The purpose of the closed loop control is to improve the dynamic performance of the microcalorimeter, resulting in an enhanced sensitivity and accuracy. The instrument performance is demonstrated by calibration experiments showing that the baseline noise (root-mean-square of the temperature difference between the cells) to be 0.4 μK and the specific sensitivity about 2–8 μJ/ml. The main time constant can be reduced from 120 s (without power compensation) to 22 s or even less (with power compensation). In a subsequent article, a precise characterization of the microcalorimeter will be given. © 2000 American Institute of Physics.