Two gamma-pyrones isolated from the seeds of Podolepsis hieracioides (Asteraceae) have been tested for their in vitro leishmanicidal activity against the promastigote form of Leishmania donovani, L. major, L. infantum and L. enriettii (IC(50)=3.76-5.43 microg/ml), and against the amastigote form of L. donovani residing within RAW 264.7 macrophage-like host cells (IC(50)=8.29-8.59 microg/ml). General toxicity of the gamma-pyrones was investigated in parallel against three mammalian cell lines (RAW 264.7, SKMel, and KB; IC(50)=11.5->25.0 microg/ml). Both compounds were not active against Trypanosoma cruzi or Trypanosoma br. brucei (IC(50)>30 microg/ml).