Histamine decreases sphincter of Oddi (SO) contractility in vivo in opossum, but increases contractility in vitro in guinea-pig. In resistor-like SO, such as in pig and man, the histamine effect is poorly known. We investigated the effect of histamine on pig SO in vivo and in vitro and on human SO in vitro. Perfusion manometry catheter and two silver electrodes for simultaneous pressure and electromyography registration were inserted into the SO transduodenally by laparotomy in six anaesthetized pigs weighing for 25-28 kg. Histamine (5-10 microgram kg-1) was infused intra-arterially (i.a.) into the pancreaticoduodenal artery with and without diphenhydramine (75 microgram kg-1) i.a. premedication. Acetylcholine (4 microgram kg-1) i.a., a potent SO stimulator, was used as positive control. After these experiments, the SO was removed and, together with seven human SO from Whipple specimens, were cut into 1.0-1.5 mm thick transverse sections (rings). The rings were placed between two hooks in oxygenated organ bath solution at 37 degrees C. The SO contraction force was measured with isometric force-displacement transducers and registered on a polygraph. SO rings were incubated with histamine (10-100 micromol L-1) and acetylcholine (100 micromol L-1) with or without diphenhydramine (10 micromol L-1), cimetidine (10 micromol L-1), or atropine (1 micromol L-1). Acetylcholine induced huge electrical bursts, and basal SO pressure increased by 20 +/- 10 mmHg. Histamine (10 microgram kg-1) induced strong SO contraction and the SO remained oedematous for over 10 min. Histamine (5 microgram kg-1) resulted in electromyographic burst activity with phasic SO contractions and increase in basal SO pressure by 34 +/- 19 mmHg for over 15 min. Diphenhydramine did not alter acetylcholine-induced SO motility, but significantly decreased histamine-induced contractions and almost abolished electrical activity. In vitro, acetylcholine induced SO contractions in pig (335 +/- 111 mg) and in man (323 +/- 54 mg). Histamine did not change SO tone in man, but in pig it induced dose-dependent contractions in the same way as acetylcholine. These contractions could be inhibited by diphenhydramine, but not by cimetidine or atropine. We conclude that histamine has a stimulatory effect, mediated by H1-receptor, on the pig SO motility. The SO response to histamine is different in adult humans from that observed in young pigs.