Abnormalities of CD40 ligand have been demonstrated in various kinds of diseases. Our objective was to determine serum soluble CD40 ligand (sCD40L) levels in patients with mixed connective tissue disease (MCTD). Serum sCD40L levels of 23 patients with MCTD and 21 healthy individuals were measured with specific enzyme-linked immunosorbent assays. Serum levels of sCD40L were significantly higher in patients with MCTD than in healthy individuals (median 0.179 ng/ml vs 0.99 ng/ml, 25th-75th percentile; 0.117-0.296 ng/ml vs 0.82-1.70 ng/ml, P<0.005), whereas there were no significant correlation between elevated serum sCD40L levels and clinical or serological features in patients with MCTD. These results suggest that sCD40L plays a role in the pathogenesis of MCTD. Further studies are needed to clarify this.