Contribution of cyclic GMP generation to the relaxation by nipradilol of vascular smooth muscle was studied in the isolated rabbit aorta contracted by phenylephrine (10(-7) M) or prostaglandin F2 alpha (PGF2 alpha, 3 x 10(-6) M). 2. Nipradilol-induced relaxation in both contractions and increase in cyclic GMP content were inhibited by methylene blue (10(-5) M). 3. The relations between the increase in cyclic GMP and the relaxation produced by nipradilol and nitroglycerin were fitted to sigmoid curves. The increase in cyclic GMP at 50% relaxation by nipradilol was smaller than that by nitroglycerin (1.2-fold increase as against 3-fold increase). 4. These results suggest a smaller contribution of cyclic GMP generation through activation of soluble guanylate cyclase to nipradilol-induced relaxation in the rabbit aorta.