Oocyte in vitro maturation (IVM) uses immature oocytes collected from small-medium sized antral follicles. It is known that the developmental potential of these oocytes can be enhanced by modulation of oocyte cAMP levels or by addition of growth factors that activate SMAD1/5/8, and that their combination is particularly important in oocytes from small follicles. Hence, we hypothesise that there is cross-talk between the cAMP/PKA and SMAD1/5/8 pathways in granulosa cells. The aim of this study was to assess the effect of the cAMP modulators used in IVM; 3-isobutyl-1-methylxanthine (IBMX; a phosphodiesterase inhibitor) and forskolin (FSK; an adenylate cyclase activator) on SMAD1/5/8 signalling activity in granulosa cells. We used the human granulosa cell line COV434 and measured SMAD1/5/8 responses using a BRE-luciferase reporter. Neither FSK (50µM) nor IBMX alone (100µM) led to activation of SMAD1/5/8, whereas FSK and IBMX together doubled SMAD1/5/8 activity (P<0.05). In a FSK dose-response experiment (0–100µM) in the presence of IBMX (100µM), SMAD1/5/8 activity was increased 4-fold following treatment with IBMX+FSK (25-100µM; P<0.05), compared to the control. When cells were treated with IBMX+FSK in the presence of a BMP type I receptor inhibitor, we observed a decrease in SMAD1/5/8 activity (P<0.05), suggesting that the IBMX + FSK treatment increases cellular SMAD1/5/8 activity through BMP ligand production. Treatment of cells with a canonical SMAD1/5/8 activator; BMP15 (5ng/mL) in the presence of IBMX (100µM) and FSK (0–100µM), led to an additive increase in SMAD1/5/8 activity when compared to BMP15 alone or with BMP15 + IBMX or BMP15 + FSK (P<0.05). These results suggest there is cross-talk between the cAMP/PKA and SMAD1/5/8 pathways in granulosa cells. This may be important for the acquisition of oocyte competence in vivo and may be one mechanism for the improvement in oocyte quality following IBMX + FSK treatment during oocyte IVM.