G0 human T cells synthesize protein at low rates and contain very low levels of eIF-2α mRNA. eIF-2α plays a pivotal role in the earliest regulated steps of translation initiation. We examined eIF-2α gene expression in normal human T cells stimulated with PHA. Nuclear run-on assays indicate low rates of eIF-2α gene transcription in G0 cells and these change 2-fold with PHA treatment. Actinomycin D chase experiments show that the t( 1/2 ) of eIF-2α mRNA is similar in G0 and PHA-treated T cells. Analysis of nuclear RNA with probes specific for eIF-2α intron sequences shows that increased eIF-2α expression after PHA treatment is largely due to intranuclear stabilization of the primary transcript. The increase in eIF-2α mRNA does not require new protein synthesis. Hence, expression of this gene appears to be a part of the primary response program of T cells when they are exposed to mitogen.