In order to clarify the role and interrelationship of c-<em>myc</em>, interleukin-2 (IL-2), and transferrin receptor (TfR) expressions on PHA-stimulated lymphocyte proliferation, we examined the effects of antisense oligodeoxynucleotides directed against c-<em>myc</em>, TfR, and IL-2 mRNAs on DNA synthesis and cell-cycle phase. Exposure of PHA-stimulated lymphocytes to each antisense oligomer resulted in approximately 75-80% inhibition of DNA synthesis. TfR expression was not inhibited in PHA-stimulated lymphocytes by c-<em>myc</em> or IL-2 antisense oligonucleotides, suggesting that the expression of c-<em>myc</em>, TfR, and of IL-2 is regulated by an independent mechanism. All three antisense oligonucleotides for c-<em>myc</em>, TfR and IL-2 synchronized mitogen-activated lymphocytes to the G1 phase as assessed by morphologic blast formation and cell-cycle phase analysis.