We have analysed the interplay of glucocorticoid receptor (GR) and the lymphocyte-specific factor Oct-2A with transient co-transfection assays. Our data confirm our previously described observation that GR and the apparently unrelated factors belonging to the Octamer family can synergize when permitted to bind in cis. However, when GR binding sites are not present in the reporter genes, we observe that the action of the cloned factor Oct-2A expressed in HeLa cells is strongly inhibited in the presence of active GR molecules. We can demonstrate that this GR-mediated inhibition of Oct-2A action is neither due to competitive binding to DNA target sites nor to a reduction of DNA binding competent Oct-2A in the transfected cells. We observe that the phenomenon is not reciprocal, since co-expression of Oct-2A does not inhibit GR-dependent transcription activation. Furthermore, we provide evidence that the observed GR-Oct-2A interference may be dependent on the type of cell line hosting the co-transfected molecules. We consider it likely that the GR-mediated inhibition is due to the exhaustion of some rate-limiting co-activators.