Siolmatra brasiliensis (Cogn.) Baill., Cucurbitaceae, commonly known as "pluméria" or "taiuiá", is widely used in different ways in Brazilian popular medicine to treat several diseases. Acute toxicity of Siolmatra brasiliensis crude ethanolic extract (CEE) was investigated in mice. No mortality or signs of CEE toxicity were observed at the doses of 10 and 100 mg/kg bw, but the administration of 1000 and 2000 mg/kg bw caused several adverse behavioral effects and mortality. Macroscopic inspection of the organs showed morphologic alterations in the heart of animals treated with doses of 1000 and 2000 mg/kg bw. According to our results, S. brasiliensis CEE has an LD50 of 1000 mg/kg bw. We conclude that S. brasiliensis CEE was safe at the doses of 10 and 100 mg/kg bw and presented toxicity at the doses of 1000 and 2000 mg/kg bw.