Kupffer cell migration and leukocyte-vessel wall interactions cause temporary slowing and/or stoppage of blood flow through individual liver sinusoids. Such temporal heterogeneity of flow was quantified in anesthetized mice and rats. Video recordings of red blood cell flow in 44 networks containing 8-16 sinusoids each were analyzed for 5- to 10-min periods. Flow was graded "fast," "slow," "stopped," or "reversed" based on red blood cell velocity. The mean numbers of flow changes (between grades) per minute in zone 1 vs. zone 3 were 1.39 vs. 0.78 (mouse) and 1.25 vs. 0.09 (rat). The mean percentage of time for each flow grade differed significantly between zones 1 and 3 and between species. For example, fast flow was present in zone 1 sinusoids for 51% of the time in mice and for 74% in rats; in zone 3 the corresponding numbers were 76 and 95%. Flow stasis was present in zone 1 sinusoids for 19% of the time in mice and for 7% in rats; in zone 3 the corresponding numbers were 2 and 0%. Thus considerable intermittence of perfusion exists, and the flow conditions create very different microenvironments for hepatocytes in zone 1 vs. zone 3.