The influence of alkyl chain length variation on the histamine H3 receptor activity of histamine homologs 1 was investigated. A series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1 was prepared with an alkyl chain length varying from one methylene group to 10 methylene groups. Besides the H3 activity, the affinities of these compounds for the H1 and H2 receptors were determined. The ethylene chain of histamine is optimal for agonistic activity on all three histamine receptor subtypes. For the H3 receptor, elongation of the alkyl chain from three methylene groups on leads to compounds with antagonistic properties. 4(5)-(5-Aminopentyl)-1H-imidazole (impentamine, 1e) is the most potent and selective H3 antagonist from this series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1, with a pA2 value of 8.4 (on guinea pig jejunum). A specific antagonistic binding site for this compound is proposed.