We have studied the endemic occurrence of chronic arsenism in a limited area on the southwest coast of Taiwan. The effects of arsenic on the mitogenic responses of mononuclear cells (MNC) derived from patients with arsenical skin cancers in that area were evaluated. The subjects enrolled in this study included patients with 1) Bowen's disease, 2) arsenical skin cancers (basal cell carcinoma and squamous cell carcinoma), 3) non-arsenical skin cancers (basal cell carcinoma and squamous cell carcinoma), 4) nasopharyngeal cancer and 5) healthy controls from endemic and non-endemic areas. Phytohemagglutinin (PHA) stimulated [3H]thymidine incorporation in MNC in all groups except the arsenical skin cancer group. However, when a low concentration of As2O3 (2.5 x 10(-7) M) was added to PHA-stimulated MNC, a tremendous amplification of the uptake of [3H]thymidine was noticed in patients with arsenical skin cancer. In this study, this phenomenon did not occur in cancers not related to arsenic. This result shows that arsenical carcinomas are hyperreactive to its specific etiology--arsenic. Arsenic seems to play a role as a co-stimulant of PHA similar to interleukin-1.