The effects of guanfacine have been studied on guinea-pig isolated atria and diethylstilboestrol-treated rat isolated uterus to determine whether it possesses histamine-like activity. Guanfacine produced a concentration-dependent negative chronotropic effect which was not modified by ranitidine (0.1 microM). In rat isolated uterus contracted by KCl, clonidine (5-5000 microM) produced concentration-dependent relaxation which was blocked by ranitidine (0.1 microM), but guanfacine only produced relaxation at high concentrations (100-1000 microM), and this was not affected by ranitidine (0.1 microM). It is concluded that guanfacine, unlike clonidine, does not produce effects due to activation of H2-receptors in either guinea-pig atria or rat uterus.