Progesterone (P) levels were acutely augmented by intravenous (IV) infusion in seven women in the midluteal phase to ascertain if short-term changes in P levels have an effect on gonadotropin secretion. During four 6-hour intervals of alternating control and IV P infusion, each subject underwent blood sampling for luteinizing hormone (LH), follicle-stimulating hormone (FSH), and P every 20 minutes for 24 hours. As a result of the P infusions, mean (+/- SE) P levels rose 72% from a control level of 26.24 +/- 2.13 to 45.22 +/- 3.47 nmol/L, whereas mean LH levels were reduced by 20% from a control level of 4.82 +/- 0.67 to 3.85 +/- 0.66 IU/L. During P infusions, mean LH pulse amplitude was reduced by 33% from 3.33 +/- 0.37 to 2.23 +/- 0.28 IU/L. The mean LH interpulse interval increased by 93% (2.56 +/- 0.14 to 4.92 +/- 0.15/h) when the interval between pulses was interdicted by the onset of P infusion. The infusion of P reduced mean FSH levels by 10% from 3.34 +/- 0.41 to 3.01 +/- 0.35 IU/L. These findings suggest that acute elevations in P levels within the physiological range have a short-term inhibitory effect on gonadotropin secretion during the midluteal phase.