The seeds of Benincasa hispida (Thunb) COGN. (Family: Cucurbitaceae) was extracted with ethanol and was used to study acute toxicity, antinociceptive and anti-pyretic effects. Brewer's yeast (15%) was used to induce pyrexia in rats. The extract was non lethal to the rats up to the dose of 5000 mg/kg b.w. At doses of 250 and 500 mg/kg b.w, the extract significantly (P<0.05) increased the antinociceptive effective in a dose dependent manner in rats. Similarly, at doses of 250 and 500 mg/kg b.w the extract significantly (P<0.05) decreased yeast-induced pyrexia in rats. These results indicate that ethanolic extract of Benincasa hispida possesses potent antinociceptive and antipyretic effects and thus pharmacologically justifying its folkloric use in the management of fever and pain conditions. © 2009 Elsevier B.V., All rights reserved.