Purified microvascular endothelial (MVE) cell preparations from guinea pig fat pad took up histamine at low concentrations by a saturable process and at high concentrations by diffusion. As noted in previous reports, MVE cell preparations from guinea pig fat pad have high histamine methyl-transferase (HMT) and diamine oxidase (DAO) activities. The present studies indicate that MVE cells inactivate histamine through: 1) the adherence of exogenous DAO from the circulation to MVE cells; 2) by the presence of DAO within the cell cytosol and 3) HMT which is present in the soluble fraction of lysed and sonified cell preparations, but may also be adsorbed to cell membrane fractions.