We have described here an algorithm to compute the partition function of the secondary structure of RNA dimers and to model in detail the thermodynamics of a mixture of two RNA species. At present, RNAcofold implements the most sophisticated method for modeling the interactions of two (large) RNAs. Because the no-pseudoknot condition is enforced to limit computational costs, our approach disregards certain interaction structures that are known to be important, including kissing hairpin complexes.