Although recent studies indicate that severe and prolonged haemorrhage, despite adequate fluid resuscitation, induces profound depression of cell-mediated immunity, the mechanisms of this remains unknown. Since macrophages (Mφ) play a key role in the development of a competent immune response by the presentation of antigens, the study investigated (i) whether the capacity of the Mφ to present antigen is altered even following mild hypotension, and (ii) what effects do different degrees of hypotension have on the Mφ-mediated processes associated with antigen presentation (i.e. the expression of Ia antigen, membrane-associated IL-1 or the secretion of IL-1). The results indicate that a minimal drop in blood pressure to ~50 mmHg (1 hr duration) was sufficient to depress Mφ antigen presentation (AP). Similarly, even a transient hypotensive episode of 15 min duration at 35 mmHg was sufficient to produce a pronounced decline in AP. Decreased AP was observed as early as 12 hr after the haemorrhagic episode (35 mmHg; 1 hr) and remained detectable for at least 120 hr thereafter. The reduction in AP capacities were qualitatively similar in both peritoneal and splenic populations, and were not attributable to surgical stress, heparinization or ether anaesthesia. Determination of IL-1 production, as well as membrane-bound IL-1 levels, in these cell populations showed no significant difference from controls. However, a significant decrease was observed in the percentage of Ia antigen (MHC class II)-positive Mφ, suggesting that reduced AP following haemorrhage may be related to the inability of these cells to express Ia.