Although it seems probable that intrahypothalamic prostaglandin (PG) E2, a cyclooxygenase metabolite of arachidonic acid, modulates interleukin-1 (IL1)-induced fever, the evidence that it plays succh a role is still only circumstantial; PGE2 does not, however, centrally mediate the fever-associated, acute-phase glycoprotein response. In this study, we investigated whether lipoxygenase products of arachidonic acid, viz. leukotriene (LT) B4, C4, D4 or E4, injected intrapreoptically (2 ng/μl, 1 μl bilaterally) induces, like IL1, febrile and acute-phase glycoprotein responses in guinea pigs; controls received pyrogen-free saline, IL1 or PGE2. Measurements were: core temperature (Tco) and, as indices of acute-phase glycoproteins, plasma levels of copper (Cu) and protein-bound N-acetylneuraminic acid (NANA). Unlike IL1 or PGE2, no LT caused a febrile rise in Tco. Similar to PGE2 but unlike IL1, no LT produced increases in the plasma levels of Cu and NANA. These results indicate that intrapreoptic LTs probably are not involved in initiating the febrile or acute-phase glycoprotein responses characteristic of IL1. © 1986.