Paraquat manufacturers in Taiwan have been found to develop solar lentigo, actinic keratosis, as well as skin cancer in sun-exposed areas. Bipyridine has been found to be the responsible agent. At present, the mechanism for the pathogenesis of bipyridine-induced skin cancer is not known and it may be multifactorial. We investigated possible alterations in tumor necrosis factor (TNF)-alpha secretion in keratinocytes treated with 4,4'-bipyridyl dihydrochloride in vitro. Normal human keratinocytes were cultured and treated with bipyridine (10 micrograms/mL) or ultraviolet B (UVB) light (10 mJ/cm2), or with a combination of both. Bipyridine treatment alone resulted in a significant reduction in constitutive TNF-alpha secretion. Furthermore, in contrast to the finding in normal keratinocytes, UVB irradiation failed to promote TNF-alpha secretion in bipyridine-primed keratinocytes.