Field stimulation relaxed the rabbit sphincter of Oddi muscle rings after incubation with atropine (1 microM) and guanethidine (4 microM) with a threefold increase in tissue cyclic cGMP content, a response previously shown to be essentially nitrergic. Preparations from hypercholesterolaemic rabbits (1.5% dietary cholesterol load over 8 weeks increasing serum total cholesterol from pre-diet 1.4+/-0.3 to 22.6+/-3.8 mmol/l) exhibited contractions with no change in cyclic GMP content under the same conditions. The nitrergic relaxation was recaptured with a twofold increase in tissue cyclic GMP content in preparations from hypercholesterolaemic rabbits undergone a treatment with 30 microM/kg farnesol i.v. twice a day over the last 3 days of the dietary period. We conclude that farnesol treatment restores nitrergic relaxation of the sphincter of Oddi in hypercholesterolaemia.