Interleukin 1 beta (IL-1) and tumour necrosis factor alpha (TNF) are important for the beta cell lysis in insulin-dependent diabetes mellitus (IDDM), while IL-1 receptor antagonist (IL-1ra) is considered protective by blocking the effects of IL-1. Serum concentrations and ex-vivo production of IL-1, TNF and IL-1ra were examined in 10 newly diagnosed IDDM (ND-IDDM) patients, and compared with 11 long-standing IDDM (LS-IDDM) patients and 14 healthy volunteers. Ex-vivo LPS-stimulated production of IL-1 in ND-IDDM patients was significantly increased compared with LS-IDDM patients and healthy controls, while TNF and IL-1ra synthesis did not differ significantly. IL-1ra/IL-1 ratio was significantly decreased in ND-IDDM, and returned to normal values in the LS-IDDM group. Circulating concentrations of IL-1ra in LS-IDDM patients were increased. These data suggest a proinflammatory imbalance in ND-IDDM patients and this may play an important role in beta cell loss.