Since interleukin (IL)-1 can modulate fetal/maternal interactions, we hypothesized that IL-1β is one potential embryonic cytokine that regulates the conceptus-induced decidual response in baboon stromal fibroblasts. Treatment of stromal fibroblasts with IL-1β (10 ng/ml, 10 min) resulted in the phosphorylation of p38 mitogen-activated protein kinase and IκB-α. This suggests that IL-1β induces multiple signaling pathways in stromal cells that result in the activation of mitogen-activated protein kinase cascade and the transcription factor NF-κB. After 4 h of stimulation, IL-1β induced gene expression of cyclooxygenase-2 (COX-2) but not cyclooxygenase-1 (COX-1). PGE₂ synthesis paralleled COX-2 messenger RNA expression. The addition of hormones [36 nm estradiol-17β, 1 μm medroxyprogesterone acetate, and 100ng/ml relaxin] to IL-1β-treated cells induced insulin-like growth factor binding protein-1 (IGFBP-1) messenger RNA expression after 3 days of incubation. A specific COX-2 inhibitor, NS 398 (10 nm), partially inhibited IGFBP-1 protein synthesis. In contrast, the induction of IGFBP-1 by N⁶, 2′-O-dibutyryladenosine 3:5′-cyclic monophosphate (dbcAMP) and hormones was not affected by NS 398 treatment. Both dbcAMP and IL-1β, in the presence of hormones, can independently induce IGFBP-1 gene expression and decidualization. However, if IL-1β and dbcAMP were added together, IGFBP-1 expression was inhibited. These data suggest that IL-1β can activate multiple signaling pathways that either positively or negatively regulate IGFBP-1 gene expression and decidualization.