A simplified method for titrations of biochemical systems is described as well as extensive error propagation through the data analysis. This work uses a Tronac Model 450 isoperibol titration calorimeter. Sample volumes of 2 ml are used and total heats of less than 5 mcal can be routinely measured. The binding of 3'-CMP to bovine pancreatic ribonuclease A is used to illustrate the methods. The binding enthalpy can be determined with a standard deviation of 1.5% and the free energy with a standard deviation of 2 to 3%.