Previous studies have shown that human T-cell leukemia virus type 1 (HTLV-1) Tax is a key molecule of synoviocyte activation in HTLV-1 associated arthropathy (HAAP). To clarify the molecular mechanism of HTLV-1 Tax-induced transcriptional activation in synoviocytes from HAAP, we investigated the role of cyclicAMP (cAMP)-regulated enhancer (CRE) binding protein (CREB)-binding protein (CBP), as a target molecule of HTLV-1 Tax. Activation of cyclic AMP (cAMP)/protein kinase-A (PK-A) pathway resulted in a significantly high response of CRE promoter in synoviocytes from patients with HAAP as well as in Tax-transiently transfected synoviocytes from patients with rheumatoid arthritis (RA). Mammalian two-hybrid analysis showed that the recruitment of CBP was responsible for CREB activation. Furthermore, PK-A activation induced CBP-Tax complex in synoviocytes from HAAP and the complex contained CREB. These findings demonstrated that complex formation of CBP and Tax is critical for enhanced CREB activity in synoviocytes from HAAP.