Addition of 8-bromo-cAMP to primary cultures of human placental cytotrophoblasts results in significant alterations in the synthesis of secreted proteins, as detected by labeling with pulses of [35S]methionine. Using immunoprecipitation techniques, we demonstrated that exposure to 8-bromo-cAMP prevented the de novo synthesis and secretion of the extracellular matrix component fibronectin, but enhanced the production of hCG subunits. The effects of the cyclic nucleotide on synthesis and secretion of these proteins were evident within 24 h. 8-Bromo-cAMP increased the cellular content of mRNA encoding the hCG alpha- and beta-subunits and prevented the increase in fibronectin mRNA, as determined by blot hybridization analysis using specific cDNA probes. These findings demonstrate that cyclic nucleotides regulate the synthesis of several specific proteins in cultured human trophoblast by regulating levels of the mRNAs encoding the proteins. The actions of cyclic nucleotides in this regard may be essential for the normal expression of trophoblast endocrine function.