The physiological function of the gallbladder (GB) is to deliver concentrated bile to the duodenum after a meal. This requires a complex coordination of the motor, secretory, and absorptive functions of the gallbladder. Control of GB motor functions involves a constant interplay between a large number of stimulatory and inhibitory hormones and neurotransmitters. With regard to intrinsic neurotransmitters, nitric oxide (NO) acts as a neurotransmitter in nonadrenergic, noncholinergic (NANC) pathways of the gallbladder. This compound has been found to inhibit GB tone and contraction in both animal and human studies. The Purpose of the present study was to examine the effects of exogenous NO donors such as glyceryl trinitrate (GTN), molsidomine (MO) and L-arginine (L-Arg) on fasting GB volume and on meal-stimulated gallbladder contraction expressed as ejection fraction (EF). The healthy subjects (13 men and 17 women), age range 19-41 years participated in this study. GB volume was examined by means of an ultrasonographic method. Volumes of GB were calculated using the sum of cylinders method as described by Dodds. EF was measured every 15 min up to a total observation period of 2 h. After recording of control values, 0.5 mg GTN was administered sub-lingually, or 4 mg MO orally or L-Arg (12.63 g of L-Arg in 300 ml of 0.9% NaCl) was infused i.v. over 120 min. It was found that the fasted GB volume was increased after GTN by 22 +/- 10% and after MO by 28 +/- 4% (p < 0.05). Post-prandial EF was reduced maximally by 22 +/- 9% (p < 0.05) after pretreatment with GTN and by 32 +/- 8% (p < 0.01) after MO. Whereas L-Arg was without any effect on resting GB, however it reduced significantly stimulated EF. These findings support the earlier knowledge that NO, released from its exogenous donors has the potent inhibitory effect on human gallbladder motor activity.