The invention relates to intracellular single domain immunoglobulins, and to a method for determining the ability of a immunoglobulin single domain to bind to a target in an intracellular environment, comprising the steps of: a) providing a first molecule and a second molecule, wherein stable interaction of the first and second molecules leads to the generation of a signal; b) providing a single intracellular immunoglobulin domain which is associated with the first molecule, said single immunoglobulin domain being free of complementary immunoglobulin domains; c) providing an intracellular target which is associated with the second molecule, such that association of the immunoglobulin domain and the target leads to stable interaction of the first and second molecules and generation of the signal; and d) assessing the intracellular interaction between the immunoglobulin domain and the target by monitoring the signal.