Interferons (IFNs) have been implicated in the aetiopathogenesis of the autoimmune disease systemic lupus erythematosus (SLE). The ability of unstimulated and Sepharose-bound concanavalin A (ConA) stimulated spleen or lymph node (LN) cells from normal CBA/T6 mice and histocompatible autoimmune strains (MRL/1, MRL/n) of various ages to produce IFN-gamma was measured. Levels of IFN-gamma produced by ConA-stimulated spleen cells from CBA/T6, MRL/1 and MRL/n mice at 6 weeks of age were not statistically different (mean +/- SEM: 786 +/- 182, 1147 +/- 282, 1024 +/- 146 IU/ml, respectively). At this age only stimulated LN cells from MRL/l mice produced detectable IFN-gamma (538 +/- 44 IU/ml) and these levels remained constant up to 6 months. IFN production by stimulated LN cells from young MRL/n mice (66 +/- 21 IU/ml at 3 months, 44 +/- 41 IU/ml at 6 months) increased at 1 year (463 +/- 97 IU/ml) corresponding to the age of disease onset. The failure of stimulated CBA/T6 LN cells to produce IFN-gamma was not due to cell-cell suppression, defective IL-2 production or the generation of soluble inhibitors. Stimulated LN cells from other normal inbred (C57Bl/6, Balb/c, A/J) outbred and FI hybrid mouse strains (Swiss, [Swiss x Balb/c] F1, (CBA/T65 x C57Bl/6]FI) produced undetectable or low levels of IFN compared to MRL/1 and MRL/n mice. These results show that autoimmune mouse LNs generate more IFN compared to normal controls and that the increase in IFN levels (at least in MRL/n) corresponds to the age of disease onset.