On the basis of molecular modelling studies the structural and conformational requirements for receptor affinity and activity of histamine H3-receptor agonists were studied. It was shown that the known H3-receptor agonists can be fitted accurately into a common pharmacophoric pattern. Using the YAK pseudoreceptor approach an amino acid model for the H3-receptor agonist binding site was generated which reflects binding properties and biological data of the investigated agonists. The postulated binding site model was validated by predicting biological data for four structures not considered in model construction. The amino acid positions of the pseudoreceptor were found to be in good agreement with calculated GRID interaction fields for the investigated histamine H3-receptor agonists.