Various mitogenic substances (concanavalin A, pokeweed mitogen, polyI : polyC and a phorbol diester), as well as lipopolysaccharides (LPS or endotoxins), produced hypoglycaemia after being injected into mice. However, non-mitogenic immuno-stimulants (zymosan, carrageenan, an adjuvant peptide and interferon) did not induce hypoglycaemia. All of the mitogenic substances also induced an increase in 5-hydroxytryptamine (5-HT) in liver, but the non-mitogenic substances did not have this effect. The time course of the development of hypoglycaemia was similar to that of the increase in liver 5-HT. The dose-dependence of the hypoglycaemia induced by LPS was similar to that of the increase in liver 5-HT. In C3H/HeJ mice, the macrophages and/or lymphocytes of the mice are known to be less responsive to LPS, and both the LPS-induced hypoglycaemia and increase in 5-HT were less in these mice than in control mice (C3H/He and ddI mice). These results suggest that macrophages and/or lymphocytes may participate in the induction of hypoglycaemia and the increase in 5-HT induced by mitogenic substances and LPS. A possible correlation between hypoglycaemia and the increase in hepatic 5-HT is discussed, although the relationship is not substantiated.