BALB/c and NZB mice differ in incidence of autoimmunological disorders. We have studied the dependence of sex and age of these mouse strains on their capacity to produce interferon beta (IFN-beta) and tumor necrosis factor alpha (TNF-alpha). Short term cultures of the mouse resident peritoneal cells (RPC) were used. Three to six week-old female and male BALB/c mice, in contrast to adult mice, did not produce spontaneous IFN-beta (< 2 units/ml) and only low level of TNF-alpha (2-4 units/ml). The levels of lipopolysaccharide (LPS)--induced IFN-beta and TNF-alpha increased progressively with age of BALB/c mice. Female BALB/c mice however, were found to produce approximately two-fold higher levels of IFN-beta and TNF-alpha than male BALB/c mice. Sex dependent differences in IFN-beta production were much more expressed when NZB mice were used in the experiments. RPC of young (3-5 week-old) female NZB mice produced relatively high levels of IFN-beta. The spontaneous IFN-beta production by RPC of older female mice (6-8 week-old) declined. In contrast, RPC of young NZB male mice did not produce spontaneous IFN-beta, while RPC of adult male mice were able to release some amounts of IFN-beta. The levels of spontaneous and LPS induced TNF-alpha and LPS induced IFN-beta were apparently not so correlated with sex and age of NZB mice as spontaneous IFN-beta.