Nerve growth factor (NGF) has recently been shown to be secreted from white adipocytes, its production being strongly stimulated by the pro-inflammatory cytokine TNF. In this study we have examined whether a series of prostaglandins and other inflammation-related factors also stimulate NGF expression and secretion by adipocytes, using 3T3-L1 cells. Although IL-1, IL-10 and IL-18 each induced a small decrease in NGF mRNA level in 3T3-L1 adipocytes, there was no significant effect of these cytokines on NGF secretion. A small reduction in NGF expression and/or secretion was also observed with adiponectin, prostaglandins PGE₂, PGF₂, and PGI₂. In marked contrast, prostaglandin PGD₂ induced a major, dose-dependent, increase (up to 20-40 fold) in NGF expression and secretion. The PGD₂ metabolites, PGJ₂ and ¹²-PGJ₂, also induced major increases (up to 30 fold) in NGF production. A further metabolite of PGJ₂, 15-deoxy-^12,14-PGJ₂, a PPAR agonist, led paradoxically to a small increase in NGF mRNA level but a fall in NGF secretion. Both PGD₂ and PGJ₂ induced significant increases in NGF gene expression by 4 h after their addition. It is concluded that PGD₂ and the J series prostaglandins, PGJ₂ and ¹²-PGJ₂, can play a significant role in the regulation of NGF production by white adipocytes. These results provide support for the view that NGF is an important inflammatory response protein, as well as a target-derived neurotrophin, in white adipose tissue.