KL-6, a mucinous high-molecular weight glycoprotein, expressed on type II pneumonocytes, is elevated in the serum of patients with active interstitial pneumonia. Forty-seven patients with histologically confirmed sarcoidosis were analyzed by chest radiography, CT, 67Ga scintigraphy, BAL fluid (BALF), and serum KL-6. Serum KL-6 level was significantly elevated in radiographic type II (945 +/- 725 U/mL; n = 13; p < 0.01) and type III (1,179 +/- 1,320 U/mL; n = 9; p < 0.01), as compared with type 0 (333 +/- 173 U/mL; n = 10) and type I (430 +/- 225 U/mL; n = 15). Serum KL-6 level was significantly elevated in patients with CT findings of irregular small opacities, ground-glass opacities, and thickened bronchovascular bundle (p < 0.01), as compared to those without these findings. Serum KL-6 level was significantly elevated in patients with positive pulmonary accumulation in 67Ga scintigraphy (1,108 +/- 1,044; n = 20; p < 0.001) as compared to those without accumulation (390 +/- 206; n = 27). Serum KL-6 level was elevated in patients with a higher CD4+/CD8+ ratio (> or =3) in BALF, as compared to those with lower ratios. These results suggest that serum KL-6 is a useful marker of sarcoidosis activity.