Predicting the secondary and tertiary structure of RNAs largely depends on our capabilities in estimating the thermodynamics of RNA duplexes. In this work, an expanded nearest-neighbor model, designated INN-48, is established. The thermodynamic parameters of this model are predicted using both multiple linear regression analysis and neural network analysis. It is suggested that due to the increase in the number of parameters and the insufficiency of the existing data, neural network analysis results in more reliable predictions. Furthermore, it is suggested that INN-48 can be used to estimate the thermodynamics of RNA duplex formation for longer sequences, whereas INN-HB, the previous model on which INN-48 is based, can be used for short sequences.