1. The involvement of histamine H3-receptors in the control of colonic motility was investigated in the rabbit. 2. In vitro spontaneous and electrically evoked contractions were evaluated in preparations of proximal and distal colon, whereas in vivo spike activity was monitored in conscious rabbits, fitted long-term with bipolar electrodes along the distal colon. 3. In vitro, selective histamine H3-receptor agonists, R(alpha)-methylhistamine and immepip (1 nM to 10 microM), and antagonists, thioperamide and clobenpropit (1 nM to 1 microM), did not modify either spontaneous motility of neurogenic contractions elicited by electrical field stimulation. In the same conditions, Neurogenic contractions were partially prevented by agonists acting at alpha2-adrenoceptors and adenosine A1- and opioid kappa-receptors. 4. In vivo, R(alpha)-methylhistamine, immepip (at both 100 and 300 microgram kg-1 i.v.) and clobenpropit (1 mg kg-1 i.v.) did not significantly affect spontaneous spike activity in the rabbit distal colon. 5. These data suggest that histamine H3-receptors are not primarily involved in the control of colonic motility in the rabbit.