Inflammatory mediators released as a result of smokeless tobacco (ST)-induced irritation may play a role in the development of oral mucosal lesions at habitual tobacco placement sites in ST users. The present study examined levels of interleukin-1 (IL-1) and prostaglandin E2 (PGE2) in ST-induced mucosal lesions and compared these to mediator levels in clinically normal mucosa. Soft tissue biopsies were obtained from white mucosal lesions at habitual placement sites and normal alveolar mucosal tissue at non-placement sites in 18 ST users. Fifteen non-tobacco using subjects also provided normal alveolar mucosal biopsies. IL-1 and PGE2 were recovered from the specimens, and mediator levels were determined by enzyme immunoassay. Prostaglandin E2 levels (pg/mg) were lower in both regions in the ST subjects, but values did not vary significantly between the regions with 2.77 +/- 0.72 and 2.86 +/- 0.99 at placement and non-placement sites, respectively, in ST users and 7.31 +/- 3.84 in non-tobacco users. Both IL-1 alpha and IL-1 beta (pg/mg) were significantly (p < 0.01) elevated in ST lesions (IL-1 alpha = 25.56 +/- 4.00; IL-1 beta = 7.76 +/- 1.68) compared to either non-placement sites in ST users (IL-1 alpha = 14.64 +/- 2.65; IL-1 beta = 1.63 +/- 0.72) or non-tobacco users (IL-1 alpha = 12.84 +/- 2.60; IL-1 beta = 2.04 +/- 0.75). In view of IL-1's role in keratinocyte proliferation and its inflammatory effects, this cytokine may contribute to mucosal and gingival alterations observed in ST users.