Human chorionic gonadotrophin (HCG) secretion by the early placenta is under multifactorial control. Epidermal growth factor (EGF) has been reported to be involved in regulating the formation and secretion of HCG by first trimester placental explants in culture. The effect of the amino-terminal fragment of parathyroid hormone (1-34 PTH), a calciotrophic factor upon HCG secretion, and its possible interaction with EGF were examined in this study, both in static cultures and in superfusion, where it has previously been demonstrated that HCG secretion is spontaneously pulsatile. Gestational age-dependent effects of 1-34 PTH were noted in both models. In static cultures, 1-34 PTH stimulated HCG secretion in 7-9 week placenta, in a biphasic fashion, the maximal effect being noted at 10-25 ng/ml concentrations (250-270%), while at 1 and 100 ng/ml, the effect was mild. In superfusion, the effect of 1-34 PTH added overnight was also stimulatory, as shown by the significantly increased pulse amplitude and area under the curve. Effects of 1-34 PTH at 11-14 weeks were inhibitory. In static cultures at 7-9 weeks, the stimulatory effect of 25 ng 1-34 PTH was increased by 70% when EGF (100 ng/ml) was added. However at 11-14 weeks, this combined effect was inhibitory. We conclude that 1-34 PTH has an endocrine effect on secretion of HCG by the first trimester placental tissue, and this effect is potentiated by the addition of EGF.