The peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor family of ligand-activated transcription factors. PPARgamma ligands have been shown to inhibit the growth of cells from different cancer lineages. This study was designed to evaluate the effects of PPARgamma receptor activation in human melanoma cell lines. The effects of its expression and activation on cell proliferation and apoptosis in human melanoma cell lines (early stage cancer [WM35] and metastatic tumour [A375]) were investigated. Reverse transcription-polymerase chain reaction and Western blot analysis showed that both human melanoma cell lines expressed PPARgamma mRNA and protein. Treatment of cells transfected with the luciferase gene ligated to PPAR response element constructed promoter showed that ciglitazone and prostaglandin J2 (PGJ2), selective ligands for PPARgamma, increased the luciferase activity, proving the induction of the PPARgamma reporter gene. Ciglitazone and PGJ2 inhibited melanoma cell proliferation in a dose-dependent manner. Analysis of the cellular morphology and apoptosis assayed by fluorescence microscopy after incubation of A375 cells with 10 micro M ciglitazone for 24 h indicated that this ligand not only inhibited cell proliferation but also induced apoptosis.