Synthesis and pharmacological characterisation of a series of products obtained by coupling the H 3 -antagonist SKF 91486 through appropriate spacers with the NO-donor 3-phenylfuroxan-4-yloxy and 3-benzenesulfonylfuroxan-4-yloxy moieties, as well as with the corresponding furazan substructures, devoid of NO-donating properties, are reported. All the products were tested for their H 3 -antagonistic and H 2 -agonistic properties on electrically-stimulated guinea-pig ileum segments and guinea-pig papillary muscle, respectively. The whole series of compounds displayed good H 3 -antagonist behaviour and feeble partial H 2 -agonist activity. Among furoxan derivatives, the benzenesulfonyl hybrid 28 , a good NO-donor, triggered a dual NO-dependent muscle relaxation and H 3 -antagonistic effect on guinea-pig intestine.