A method of screening for compounds that module expression of specific macromolecules, the “target”. The method is particularly useful in that it does not require separation of target-bound and excess ligand and therefore enables, but is not limited to, High Throughput Screening for compounds that increase or decrease the levels or amounts of a target present in a biological sample. The method can also be used for high-throughput diagnosis of a condition leading to an increase or decrease of a cellular macromolecule.