Interleukin 6 (IL-6) is a multi-functional cytokine which has a major role in tissue damage. It is secreted by many types of cell, including oral fibroblasts, and has been implicated in the pathogenesis of periodontal diseases, particularly those associated with sex hormones. In the present study we investigated whether the androgen dihydrotestosterone (DHT) affects the expression and regulation of IL-6 in gingival fibroblasts. Using a 'capture' ELISA assay, it was found that increasing DHT concentrations progressively reduced IL-6 production by gingival cells from normal individuals and from patients with gingival inflammation and gingival hyperplasia. In contrast, cells from periodontal ligament tissue produced only barely detectable levels of IL-6. The anti-androgen cyproterone acetate acted as an androgen analogue in the gingival fibroblasts, potently inhibiting IL-6 production, and did not reverse the DHT-mediated downregulation of the cytokine. Flutamide also failed to abrogate DHT inhibition of IL-6 production, and it had no effect on IL-6 production in the absence of DHT. Moreover, semi-quantitative RT-PCR showed that DHT acted at the level of transcription of the IL-6 gene, causing a marked reduction in the relative level of IL-6 mRNA in the gingival cells.