In the search for biologically active compounds from Euphorbia lagascae Spreng, an herbaceous plant native to southeast of Iberic Peninsula, a stilbene, two coumarins and two 1-2-deoxyphorbol diterpene esters were isolated by chromatographic methods, from the methanol extracts of its defatted seeds. The structures of these compounds were elucidated by a combination of physical and spectral data (IR, MS and high-resolution (1)H-NMR and (13)C-NMR spectroscopy utilizing COSY, HMBC, HMQC and NOESY experiments). The stilbene, piceatannol, was screened for its antileishmanial activity against promastigotes as an extracellular form of Leishmania donovani, Leishmania infantum and Leishmania major, and amastigotes of Leishmania donovani as an intracellular form. Pentostan((R)) (sodium stibogluconate), the first line clinical drug, was used as a standard reference. Piceatannol was moderately active against the extracellular forms of the three tested Leishmania species, and more active than the reference compound against the intracellular form of Leishmania donovani. Copyright (c) 2007 John Wiley & Sons, Ltd.