The scanning electron microscopic was used to study the fenestrations of human liver sinusoids. Thirteen biopsies, where light microscopy and transmission electron microscopy revealed normal sinusoidal architecture, were investigated. The number of fenestrae was calculated in acinar zone 3 and acinar zone 1 areas. The porosity, i.e. fenestrated area relative to total area of the sinusoidal lining wall, was estimated on micrographs by using a Texture Analysing System (TAS). A zonal gradient was found with median 23.5 fenestrae per micron 2 in zone 3, as compared to 19.2 fenestrae per micron 2 in the zone 1 area (p less than 0.005). Increasing porosity towards the terminal hepatic vein was found (9.1% in zone 3 vs. 7.6% in zone 1 (p less than 0.05)). This was due to an increased number of fenestrae measuring 100 nm or less in diameter in zone 3 areas. The number of fenestrae measuring more than 100 nm but less than 300 nm was unchanged along the sinusoids. Fenestrae larger than 300 nm were rare and randomly distributed. The results suggest a different permeability along the sinusoidal lining, which may influence the transport between blood and hepatocytes and thus be of importance to hepatocellular function.