We were able to rapidly determine the susceptibility of human cytomegalovirus to ganciclovir using a late antigen synthesis reduction assay directly on primocultures of clinical specimens. This test was compared with a conventional susceptibility assay which was performed with cell-free virus obtained after cytomegalovirus isolation and in vitro passages. Both tests produced similar results. The rapid test, unlike conventional assays, is able to provide a result within 5 days after receipt of the specimen and could thus play a direct role in the therapeutic decision.