1 Previous observations that centrally injected interleukin-lB (IL-iI) into rabbits induces a sustained rise in cerebrospinal fluid (CSF) Ca2+ concentration ([Ca2+]) as well as fever, prompted us to undertake an in vitro study to corroborate the in vivo results and gain insight as to the source and mechanism of IL-1/I-induced Ca2+ mobilization. 2 IL-1I treatment of rat striatal slices preloaded with 45Ca2 + elicited a rise in spontaneous 45Ca2+ release which was dose-dependent, delayed in onset and of extended duration. At concentrations of 1, 5 and 10 ng ml-', the 45Ca2+ efflux increased by 6.3+1.3 (s.e.mean), 33.4+5.0 and 159+10.5% respectively. 3 At 1 Mg ml-', the specific IL-I receptor antagonist, IRAP, antagonized the effect induced by, 10 ng ml-' IL-i. 4 Caffeine 10 mm, which failed to release calcium on its own, potentiated IL-1-elicited 45Ca2+ release. 5 Perfusion with a Ca2+ -free medium obtained by use of excess EGTA (3 mM) or in the presence of the Ca2+ channel blocker, nifedipine (3 x 10-8 M) abolished the potentiating effect of caffeine without affecting the IL-i-induced 45Ca2+ release. 6 Preincubation of slices for 4 h with Bordetella pertussis toxin (PTX, 1.3 yg ml') did not change the pattern of Ca2+ efflux in response to In conclusion, these data indicate that IL-I stimulates calcium release from brain tissue by a specific, receptor-mediated mechanism which partly depends on extracellular calcium but does not involve a PTX-sensitive G protein as part of the transducing signal.