Tumour necrosis factor-α (TNF-α), interleukin-6 (IG6), IL-1 and transforming growth factor-β (TGF-β) have been recognized as important mediators of pathophysiological and immunological events associated with shock. Previous studies have indicated that although peritoneal macrophage (PM∅) antigen presentation was depressed following haemorrhage, the cytokine release capacity in response to lipopolysaccharide (LPS) was not affected in vitro. To determine the effect of haemorrhagic shock on PM∅ cytokine mRNA transcription, 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. PM∅ were isolated at 1 or 24 hr after haemorrhage and were incubated without or with 10 μg LPS/ml for 1 hr. Total RNA was then extracted followed by Northern blot analysis, as well as semi-quantitative reverse transcription and polymerase chain reaction (RT-PCR). The results of Northern blot analysis indicated that haemorrhage markedly increased LPS-induced IL-1β, IL-6, and TNF-α mRNA accumulation in PM∅ at both 1 and 24 hr after haemorrhage and resuscitation. Furthermore, competitive RT-PCR demonstrated that mRNA of IL-1β, IG6, TNF-α, as well as TGF-β, was increased in PM∅ obtained 1 hr after haemorrhage either with or without LPS stimulation. The data from Northern blot analysis and semiquantitative RT-PCR also revealed that LPS enhanced the effect of haemorrhage on PM∅ cytokine gene expression. Thus, following haemorrhage, PM∅ showed elevated cytokine mRNA accumulation which was not followed by an increased ability to release cytokines in response to LPS in vitro. These results, therefore, suggest that different mechanisms regulate gene expression and subsequent cytokine secretion by PM∅ following haemorrhage.