The hypothesis that inhibitory effects of isoprenaline on myometrial contractility may be constrained by activation of putative intracellular beta-adrenoceptors negatively-coupled to adenylate cyclase was examined. Field-stimulated preparations of guinea-pig and human myometrium were used to examine the influence of the catecholamine extraneuronal uptake2 inhibitors, corticosterone and beta-oestradiol, on the inhibitory effects of the beta-adrenoceptor agonist, isoprenaline, on uterine contraction. Longitudinal and circular myometrial layers were obtained from guinea-pigs in dioestrus, primed with oestrogen before progesterone, or pregnant (Days 62-65). In the guinea-pig myometrium, corticosterone (30 microM) did not affect responses to isoprenaline. beta-oestradiol (10 microM) induced a small potentiation of the effects of isoprenaline on longitudinal myometrium from dioestrus guinea-pigs. Myometrial preparations were obtained from pregnant women (36-40 weeks gestation) undergoing caesarean section. Isoprenaline inhibited stimulation-evoked contractions in 7 of 10 preparations of the inner myometrial layer and in 5 of 8 preparations of outer myometrial layer. Corticosterone (30 microM) reduced the effects of isoprenaline on the inner layer and did not affect the outer layer. These results do not support the existence of mechanism involving isoprenaline-sensitive intracellular receptors which constrain responses to beta-adrenoceptor agonists.