In myometrium from pregnant rats, 100 nM-TPA elevated resting tension and initially slightly enhanced the contraction induced by 138 mM-KCl. After 20 min this force development significantly declined. In saponin-treated skinned myometrial cells from pregnant rats, 100 nM-TPA enhanced the contraction induced by 0.3 microM-Ca2+, but reduced that induced by 1 microM-Ca2+. These findings suggest that the excitatory and inhibitory actions of TPA on the myometrium are probably due to its action on the contractile proteins. In myometrium from non-pregnant rats, TPA affected neither the resting tension, nor the amplitude of the evoked contractions, nor the Ca2+-induced contractions in skinned myometrium. While TPA only affected tension development in pregnant rats, both 1 mM-carbachol and 90 nM-oxytocin induced a tonic contraction in Ca-free solution independently of the hormonal status of the rats. The latter finding makes it unlikely that activation of protein kinase C is involved in the agonist-induced tonic force development in Ca-free solution.