Abstract: Algorithms for exchange of kidneys is one of the key successful applications in market design, artificial intelligence, and operations research. Potent immunosuppressant drugs suppress the body's ability to reject a transplanted organ up to the point that a transplant across blood- or tissue-type incompatibility becomes possible. In contrast to the standard kidney exchange problem, we consider a setting that also involves the decision about which recipients receive from the limited supply of immunosuppressants that make them compatible with originally incompatible kidneys. We firstly present a general computational framework to model this problem. Our main contribution is a range of efficient algorithms that provide flexibility in terms of meeting meaningful objectives. Motivated by the current reality of kidney exchanges using sophisticated mathematical-programming-based clearing algorithms, we then present a general but scalable approach to optimal clearing with immunosuppression; we validate our approach on realistic data from a large fielded exchange.