Abstract: One aspect of the invention is the method of operating a microphysiometer including a plunger assembly having a plunger body with a microchamber at one end for receiving a sample and a passage in the plunger body communicating with the microchamber comprises passing a medium transversely through the-sample in the microchamber. Another aspect of the invention is the construction of the plunger assembly wherein the sample is positioned in the microchamber and the passage and microchamber are constructed and arranged so that medium flow is transverse through the sample. The sample may be a tissue slice retained between a pair of screens or membranes, adherent cells on a mesh screen or non-adherent cells retained in a chamber defined by a washer and a pair of screens or membranes.