The serum levels of squamous cell carcinoma associated antigen (SCCA) were determined by a microparticle enzyme immunoassay in a group of patients with stage I oral squamous cell carcinoma (OSCC), major or minor type erosive oral lichen planus (EOLP), recurrent aphthous stomatitis (RAS), Behçet's disease (BD), oral leukoplakia (OL), or oral submucous fibrosis (OSF), and in normal control subjects. About 97% of the normal control subjects and the patients with minor type EOLP, RAS, BD, OL or OSF had a serum level of SCCA within the normal limit of 1.2 ng/ml. However, 6 of the 12 (50%) patients with stage I OSCC and 14 of the 31 (45.2%) patients with major type EOLP had a serum level of SCCA greater than 1.2 ng/ml. The mean serum level of SCCA in stage I OSCC patients (1.38+/-1.16 ng/ml) or in major type EOLP patients (1.32+/-1.23 ng/ml) was significantly higher than that in normal control subjects (P<0.001) and that in the patients with minor type EOLP (P<0.001), RAS (P<0.001), BD (P<0.05), OL (P<0.05), or OSF (P<0.05). Either major or minor type EOLP patients could obtain a significant mean reduction of the serum SCCA level of 0.34-0.63 ng/ml after treatment with levamisole and/or Chinese medicinal herbs for 1-30 months. Combination therapy with levamisole plus Chinese medicinal herbs could achieve a shorter duration of treatment to get complete remission than the single therapy with either levamisole only or Chinese medicinal herbs only. We conclude that levamisole and/or Chinese medicinal herbs can modulate the serum SCCA level in EOLP patients. SCCA may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of EOLP. For EOLP patients, the combination therapy is superior to the single therapy of levamisole or of Chinese medicinal herbs.