Peroxisome proliferator-activated receptor gamma (PPARgamma) activation by its ligands reportedly inhibits monocyte function. However, because the concentrations of PPARgamma ligands used in previous studies were higher than typically expected to activate PPARgamma, we clarified whether PPARgamma ligands influence monocyte function and cell viability of the human monocyte cell line THP-1. We determined tumor necrosis factor-alpha (TNF-alpha) release as a monocyte function and cell viability using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide. Both troglitazone and 15-deoxy-delta12,14-prostaglandin J2 (15-d-PGJ2) seemed to inhibit phorbol ester-induced TNF-alpha release from THP-1 cells. On the other hand, neither pioglitazone nor rosiglitazone inhibited phorbol ester-induced TNF-alpha release. Because the cytotoxicity of troglitazone and 15-d-PGJ2 was significantly (p<0.05, Tukey-Kramer) stronger than that of pioglitazone and rosiglitazone, the inhibition of TNF-alpha release seemed to parallel the lack of cell viability. We concluded that PPARgamma ligands did not directly inhibit TNF-alpha release in THP-1 cells.