Summary:Hydrocortisone (HC) distribution over the three main components of blood, i.e., plasma water, plasma proteins, and erythrocytes, was studied in vitro at various HC concentrations in plasma, in a suspension of washed erythrocytes in plasma water, and in whole blood. The distribution ratio of HC in the system of erythrocytes in plasma water was 2.1 when HC, 0.18‐10.8 &mgr;g/ml, was added. In whole blood, however, this ratio was 2.4 for the same concentration range. In the HC range of 0.18‐0.68 &mgr;g/ml of whole blood, the uptake percentage of HC by erythrocytes increased from about 16 to 28% of the amount of HC added. By adding blank ultrafiltrate to HC‐enriched blood, it appeared that the erythrocyte fraction released HC in overproportional quantities compared with the release by plasma proteins. Similar findings have previously been reported regarding the drugs valproic acid and phenytoin. Migration of HC from HC‐spiked plasma to blank erythrocytes reached an equilibrium within 5 min.