1. Circulating corticosterone, interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF alpha) activities in serum of Lewis and Wistar rats were measured following injection of lipopolysaccharide (LPS). IL-1 was measured as 'lymphocyte activation factor' (LAF) activity following precipitation of inhibitory activity with polyethylene glycol. TNF alpha activity was measured as cytotoxic activity. 2. Compared to the Wistar, the Lewis rat had higher circulating LAF and TNF activities following LPS, and release of both cytokines was prolonged in this strain. 3. Corticosterone increases in response to LPS were less in the Lewis than in the Wistar rat following the initial peak at 1 h; basal corticosterone was lower in the Lewis rat. 4. Adrenalectomized Lewis rats had even greater amounts of circulating LAF and TNF activities following LPS than did intact animals; the effect of adrenalectomy was not however mimicked by acute treatment with the steroid receptor antagonist, RU486, suggesting that endogenous corticosteroids did not acutely control cytokine release. 5. Although in vivo administration of anti-murine IL-1 alpha antiserum significantly lowered LAF activity of serum, circulating corticosterone in response to LPS was not affected. Similarly, treatment with anti-murine TNF alpha monoclonal antibody (mAb) abrogated TNF activity without affecting corticosterone, suggesting that other mediators may be responsible for corticosterone release following LPS. 6. This 'overproduction' of inflammatory cytokines together with lower circulating corticosterone may contribute to the susceptibility of the Lewis rat to diseases such as adjuvant arthritis or experimental allergic encephalomyelitis.