In vitro nuclear binding of the ( 3H) dexamethasone-receptor complex from rat liver cytosol takes place at a slow rate when nuclei are incubated at low temperature. However, if theophylline is included during the incubation there is a threefold increase in the rate of nuclear binding. The activation by theophylline is independent of its known effect on cyclic AMP levels since the cyclic nucleotide has no effect on nuclear binding either in the absence or presence of theophylline. Activation ability is specific to methylxanthines and not to nucleoside derivatives. Theophylline may be acting directly on the ( 3H) dexamethasone-receptor complex converting it to an active form.