A new type of H1-agonists resulted from the combination of the essential histamine structure with parts of H2-antagonists. 2,4-Disubstituted imidazole derivatives were synthesized by reaction of imidic acid methyl esters with 1,3-dihydroxypropanone, 1,4-dihydroxybutanone or 2-oxo-4-phthalimido-1-butylacetate in liquid NH3. The imidazole intermediates were converted into histamine analogues by simple deprotection, Gabriel synthesis followed by deprotection, or by side-chain elongation via the nitriles and final hydrogenation. The new compounds were screened for H1-activity on the isolated guinea-pig ileum and for H2-antagonistic activity on the isolated guinea-pig right atrium. The substances are comparably weak H1-agonists and moderate H2-blockers.