CD40 ligand (CD40L) is expressed by activated T cells and interacts with the CD40 molecule present on B cells and endothelial cells, promoting immunoglobulin switching in the former and cytokine upregulation in the latter. CD40L exists in both a soluble (sCD40L) and a membrane-bound form. Because primary biliary cirrhosis (PBC) is characterized by targeting of small intrahepatic bile ducts by autoreactive T cells, plasma concentrations of sCD40L were investigated using enzyme-linked immunosorbent assay (ELISA) to measure plasma concentrations of sCD40L in 12 patients with PBC and 12 healthy controls. No difference could be detected between plasma concentrations of sCD40L in patients versus controls (P = 0.977). No correlation between age and plasma levels of sCD40L could be identified (P = 0.24). We concluded that PBC patients do not exhibit higher plasma concentrations of sCD40L than age-matched controls, a finding common to several autoimmune diseases. Further investigation of the CD40-CD40L system is strongly encouraged.