Membrane fractions prepared from the uterine endometrium of untreated ovariectomized sheep contained a 41 x 10(3) Mr protein that was [32P]ADP-ribosylated by pertussis toxin in the presence of [32P]NAD. Progestin and progestin plus oestrogen treatment in vivo increased the concentration of this protein 2.7- and 3.6-fold respectively. Endometrial extracts from untreated or progestin-treated sheep also contained proteins of Mr 69 x 10(3) and 120 x 10(3) which were ADP-ribosylated in the absence of pertussis toxin; these proteins were not ADP-ribosylated in sheep receiving oestrogen. Incubation of endometrial slices from progestin plus oestrogen-treated sheep with oxytocin in vitro increased phosphoinositide hydrolysis 11-fold. This effect was not altered by prior incubation with pertussis toxin, although toxin treatment reduced by 64% subsequent labelling of the 41 x 10(3) Mr protein when membrane fractions prepared from pretreated slices were incubated with pertussis toxin and [32P]NAD. Thus the endometrium contains a pertussis toxin-sensitive protein which is induced by steroid treatment, but this protein is not involved in the phosphoinositide response to oxytocin.