Tumour necrosis factor-alpha (TNF) stimulates cytomegalo-virus (CMV) activity in a transfected human monocytic cell line. We assessed whether this finding is relevant in vivo by evaluating the frequency of active CMV infection in patients with diseases that enhance plasma TNF, in septic disease, peripheral blood mononuclear cells of almost all patients studied were positive for CMV. Furthermore, CMV antigenaemia and enhanced plasma TNF occurred in many patients with liver cirrhosis, common variable immuno-deficiency, and B-cell chronic lymphocytic leukaemia. Thus, TNF may have a central role in CMV reactivation.