Progesterone treatment of estrogen-primed chicks leads to a shift in the oviduct polysome profile and an increase in the proportion of cytoplasmic RNA which is ovalbumin mRNA. To determine whether the progesterone effect is primarily transcriptional or translational and whether it is separable from estrogen action, rapid estrogen withdrawal by the anti-estrogen tamoxifen was compared in the presence and absence of progesterone. After estrogen stimulation, 24 h of tamoxifen treatment causes ovalbumin synthesis and ovalbumin mRNA levels to fall 10-fold. The proportion of ovalbumin mRNA in the monosome and supernatant fractions of the polysome profile increases; however, these sequences can associate with polysomes if elongation is inhibited by cycloheximide. Progesterone prevents the tamoxifen effects, even if administered 9 h after tamoxifen (at which time ov mRNA has decreased by 30%). The progesterone-induced increase of ovalbumin mRNA (from 0.64% of cytoplasmic RNA to 0.79%) and the increased proportion of ribosomes in polysomes (from 65% to 80%) are thus independent of estrogen action. Twenty-four hours of progesterone plus tamoxifen treatment enhances initiation of translation. However, after prolonged treatments of several days, translation becomes inefficient: ovalbumin synthesis falls by 30% without a coordinate decrease in ovalbumin mRNA, and a significant proportion (15%) of the ovalbumin mRNA becomes localized in monosomes. Thus, optimal maintenance of oviduct mRNA utilization requires the presence of estrogen.