In Taiwan there is a significant correlation between oral precancer diseases and oral cancer associated with the betel quid chewing habit. The carcinogenic components of betel quid are arecoline, arecaidine and safrole. However, it is unknown whether these substances influence the immune functions. This study investigated the effects of betel quid on the immune system using cultured peripheral blood mononuclear cells from patients with oral mucous diseases. In our experiment, mononuclear cells from 10 normal persons, 12 patients with precancer lesions, and 16 patients with squamous cell carcinoma were separated from blood samples and cultured. After stimulation by arecoline, the amounts of IL-2, TNF-alpha, TGF-beta and IFN-gamma secreted by mononuclear cells were measured using the ELISA method. The results showed that IL-2, TNF-alpha, and TGF-beta were significantly lower in mononuclear cells of normal persons as stimulated by arecoline. The TGF-beta amount in cells from oral submucous fibrosis patients with betel quid chewing habit (OSF-B) was lower than normal persons or patients who had long term betel quid chewing habit but were without oral mucosal diseases (N-B), and was also lower than the squamous cell carcinoma with betel quid chewing group (SCC-B). TNF-alpha was significantly lower in the squamous cell carcinoma with long term betel quid chewing group (SCC-B) than in normal persons. TNF-alpha was significantly higher in the squamous cell carcinoma without betel quid chewing group (SCC-N) than in normal persons and SCC-B groups. In addition, IFN-gamma was significantly lower in patients who had long term betel quid chewing but were without oral mucous lesions than the normal person and the OSF group. The results proved that betel quid influences cytokines production by mononuclear cells.