The hepatic portal vein (HPV) is a rhythmically active blood vessel situated between the gastrointestinal tract and the liver that supplies 80% of the blood perfusing the liver. Whilst the generation of spontaneous activity by PVs from different species is well documented there is no information on the regulation of this activity by dietary factors. The present study investigated whether there was any influence of food intake on the spontaneous activity of HPV from adult balb-C mice. HPVs were harvested from fed animals or mice deprived of food for 16 h (fasted) and humanely killed. HPVs were mounted for isometric tension recording in standard tissue baths containing Krebs solution at 37^oC and aerated with 95%O2/5%CO2. All tissues studied were spontaneously active within 10 mins of mounting. In HPVs from fed animals the activity exhibited a number of different contractile patterns ranging from single contractions to bursts of contractions whereas in all HPVs from fasted animals only single contractions were recorded. The mean interval between contractions was significantly longer in HPVs from fed animals (6.3 ± 0.2 s compared to 4.7 ± 0.12 s, mean ± SEM, p = <0.001, data from 25 and 14 animals respectively). The duration of individual contractions was also briefer in HPVs from fasted mice (4.2 ± 0.09 s v 5.74 ± 0.22 s, p<0.001, Student's t test) and individual contractions were significantly smaller (0.1 ± 0.02 g compared to 0.18 ± 0.01, p <0.01). In comparison the effects of exogenously applied phenylepherine and 5-HT (100 μM) were not significantly different between both groups. However the maximal response to 60 mM KCl was smaller in HPVs from fasted mice (0.17 ± 0.02 g compared to 0.21 ± 0.02, p <0.05, n=9 and 14). These data show that food deprivation has a profound effect on PV rhythmicity.