The clinical significance of L-fucose was investigated in serum of a well characterized cohort of 135 RA patients and 60 healthy controls. In RA patients, serum L-fucose was significantly decreased to a mean of 5.57 +/- 0.97 mg%, (range 2.2-7.5 mg%), compared with 7.5 +/- 1.04 mg% (range 5.7-9.8 mg%) (p < 0.001) in normal controls. In early RA serum L-fucose was significantly depressed to a mean of 6.08 mg%, a value which was significantly higher than the mean concentration of L-fucose in patients with advanced RA. Serum L-fucose was significantly correlated with the rheumatoid disease activity, duration, number of involved joints, and bone erosions. No statistically significant difference was found between seropositive and seronegative RA patients. However, a significant difference (p < 0.001) between female (5.57 mg%) and male (6.59 mg%) patients with advanced RA, and between male (6.08 mg%) and female (5.99 mg%) patients with early RA was found. These findings suggest that serum L-fucose is depressed in patients with rheumatoid arthritis, a promising observation since L-fucose is a safe and simple natural sugar. It may be used as an additional parameter and as an indicator for the disease activity in the follow up of patients with rheumatoid arthritis.