The occupational importance of tellurium and selenium is growing rapidly, but the biochemistry of exposure is poorly understood. Here we report the potential toxic effects of diphenyl diselenide (PhSe)(2), diphenyl ditelluride (PhTe)(2) and Ebselen in rats and mice. The results suggest that (PhTe)(2) is more toxic in rats than mice. (PhSe)(2), (PhTe)(2) and Ebselen are more toxic by intraperitoneal (i.p.) than subcutaneous (s.c.) route. Calculated LD(50) for (PhTe)(2), i.p., was 0.65 micromol/kg in rats and 150 micromol/kg in mice, and LD(50), s.c., was 0.9 micromol/kg in rats and >500 micromol/kg in mice. Calculated LD(50) for Ebselen, i.p., was 400 micromol/kg in rats and 340 micromol/kg in mice and LD(50), s.c., was >500 micromol/kg in both mice and rats. (PhTe)(2) at small doses increased 2-fold serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in rats. LD(50) for all organochalcogens administrated in mice inhibited blood delta-ALA-D activity. The present study provides evidence for liver and renal toxicity of (PhTe)(2).