The purpose of this study was to determine whether withdrawal from chronic exposure to the female sex steroid progesterone (P) alters response of female rats to an electrified prod using the defensive burying paradigm, considered a rat model of anxiety. Withdrawal from chronic exposure to 500 micrograms P (daily, SC, for four days) resulted in a significant decrease in the latency (77%, P < 0.05) to prod burial and an increase in duration (75%, P < 0.05) of this reflexive response, compared with the behavior of oil-injected controls. These results are consistent with the idea that withdrawal from chronic exposure to P increases behaviors that accompany anxiety. At a lower dose (50 micrograms), withdrawal from chronically administered P produced significant changes in response to this paradigm only when the steroid was given concomitantly with estradiol (2 micrograms, SC, for two days). Prior exposure to indomethacin, which blocks the conversion of P to its metabolite 3 alpha,5 alpha-tetrahydroprogesterone (3-alpha-hydroxy-5-alpha-pregnan-20-one), prevented P withdrawal from altering response in the defensive burying paradigm. This finding suggests that it may be withdrawal from this metabolite, rather than P, which increases behaviors associated with increased anxiety.