The effects of cytomegalovirus (CMV) infection on monocyte and T cell activation and the role of the tumor necrosis factor (TNF) system and interleukin (IL)-10 were studied in a prospective study of 25 renal transplant recipients. Ten patients developed CMV disease (group A), 5 developed asymptomatic infection (group B), and 10 did not have CMV infection (group C). During CMV disease (group A), there was evidence of both monocyte and T cell activation. All patients with CMV infection (groups A and B) showed increased activation of the TNF system, concomitant with an increase in plasma levels of IL-10. Patients with CMV disease (group A) had more marked manifestations of TNF activation and more moderate IL-10 increase than patients with asymptomatic CMV infection (group B), reflected in a higher plasma IL-10/TNF-alpha ratio in asymptomatic patients. Thus, the balance between TNF-alpha and IL-10 may be important in the development of CMV infection and CMV-related disease.