The effects of retinoic acid (RA) on the cell growth and expression of interleukin-2 (IL-2) receptor (IL-2Rα/p55,Tac, CD25) by the human T lymphotropic virus type I positive (HTLV-I(+)) T cell lines, HUT102 and ATL-2,were investigated. Incubation of these cells with RA resulted in marked growth inhibition and down-regulation of CD25 expression. Four clones of HUT102 cell lines were established by limiting dilution, and RA was shown to inhibit the growth and CD25 expression in three of these clones, but in the fourth. However RA did not induce growth inhibition of the HTLV-I-negative T cell lines, MOLT-4 and Jurkat, and of normal lymphocytes that had been stimulated wih phytohemagglutinin. We hydothesized that the sensivity to retinoids depends on an imhalance in intracellular redox potential. To examine the effect of exogenous thiol compounds for the growth inhibition of HTLV-I(+) T cell lines induced by RA, these cell lines were cultured with serveral thiol compounds (ATL-derived factor, thioredoxin, L-cystine and glutathione (GSH)), following the addition of RA in thiol-free medium. Unexpectedly, thiol compounds alone, when added after RA, did not restore the growth inhibition of HTLV-I(+) T cell lines induced by RA. However, when those cells were preincubated with thiol compounds for 24 hrs, no RA-induced growth inhibition was observed. These findings suggest that intracellular reductive environments induced by thiol compounds are associated with resistance to RA of HTLV-I(+) T cells, and that thiol compounds may play an important role in HTLV-I(+) T cell proliferation.