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A differential solution microcalorimeter with a mixing system is described. Up to 1 ml of reagent A may be mixed with up to 3 ml of reagent B in less than 1 sec with a heating artifact of less than 0.5 mcal. A temperature range of 0 to 40°C has been utilized with a 2 h temperature equilibration time. The time course of biochemical reactions has been followed for up to 1 h. Computer simulation of the calorimeter permits data correction for heat conduction losses. For reaction heats greater than 25 mcal, ΔH and the rate constant of the reaction may be determined to ±2%. Detectivity is ±20 μcal. A digital computer simulation technique based on a finite‐element analysis of heat conduction, which is of general applicability, was developed to correct the output data for heat conduction losses.