TNF-α, IL-1, IL-6 and TGF-β are important macrophage-derived mediators which play the pleiotropic role in inflammatory, metabolic, hematopoietic and immunologic processes. Studies have shown that haemorrhagic shock without significant tissue trauma induces profound immunosupression which is associated with elevated plasma levels of TNF-α IL-1, IL-6 as well as TGF-β. Furthermore, Kupffer cells but not the splenic Mφ isolated from post-haemorrhaged animals showed an increased capacity to release inflammatory cytokines in response to LPS stimulation in vitro. However, it remains unknown whether the innate (i.e. in the absence of LPS stimulation) cytokine genes expression in Kupffer cells and splenic Mφ is affected by haemorrhage. To determine this, C3H/HeN male mice were bled to and maintained at a mean arterial blood pressure of 35 mmHg for 60 min, and then adequately resuscitated. Splenic macrophages and Kupffer cells were isolated at 1 h after haemorrhage. Total RNA was extracted and cytokine mRNA was detected by semi-quantitative reverse transcription and polymerase chain reaction (RT-PCR). The results demonstrate that haemorrhage significantly elevated the mRNA accumulation of TNF-α, IL-1β, TGF-β while IL-6 gene expression in Kupffer cells and splenic Mφ was only slightly increased. Since Kupffer cells but not the splenic Mφ showed increased cytokine release, it could he concluded that the differential regulation of cytokine release by these two macrophage populations following haemorrhage may be due to the divergence of the cytokine at the translational level. This difference between splenic Mφ and Kupffer cells might due to the different cellular composition, anatomical location and physiological environment in which these two fixed tissue macrophage populations reside. © 1995 Academic Press, Inc.