The toxicity of cinnabar, a naturally occurring mercury sulphide (HgS), has long been referred to soluble mercury chloride (HgCl2 ). To investigate whether the speciation of mercury plays a role in its disposition and toxicity, we hereby investigated and compared cinnabar with soluble HgCl2 and pure insoluble HgS in mice on mercury absorption, tissue distribution and in relation to the biological effects. The male C57BL/6J mice were treated by oral administration of various doses of cinnabar, with 0.01 g/kg of HgCl2 for comparison, or the same dose of cinnabar or pure HgS (0.1 g/kg), once a day for 10 consecutive days. The total mercury contents in serum and tissue (brain, kidney, liver) were measured by atomic fluorescence spectrometer (AFS). The biological effects investigated involved monoamine neurotransmitters (serotonin, 5-HT) in brain as an indicator of therapeutic function, and serum alanine transaminase (ALT) as a marker of hepatic damage, blood urea nitrogen (BUN) and serum creatinine as markers for renal function. The mercury absorption of cinnabar or HgS was much less than that of HgCl2 . The mercury levels in brains of the cinnabar group were only slightly changed and kept in a steady-state with the dose elevated. Cinnabar or HgS suppressed brain 5-HT levels. HgCl2 could not cause any changes in brain 5-HT although the mercury level increased considerably. The results revealed that cinnabar or HgS is markedly different from HgCl2 in mercury absorption, tissue distribution and influence on brain 5-HT levels, which suggests that the pharmacological and/or toxicological effects of cinnabar undertake other pathways from mercuric ions.