The relations between the concentrations of a drug in the blood (plasma, haemoglobin, red blood cells (RBCs), RBC membranes) and in the brain tissue (homogenate, membranes, cytosol) were investigated during chronic administration of imipramine. Radioimmunoassay was employed to measure the antidepressant concentrations. The concentrations were measured and analysed in 40 rats receiving various doses of imipramine. The concentration of total imipramine (imipramine + desipramine) in erythrocyte membranes (ghosts) amounted to 79.4 +/- 4.6% (mean +/- S.E.M., N = 40) of those measured in intact RBCs. Marked accumulation of the drug in the brain tissue, especially in brain cell membranes, was confirmed. The concentrations in brain tissue homogenate was found to be 14.8 times higher than that in RBCs. Values in brain membranes were 10.9 times higher than that in blood element membranes. There is a significant association between the concentrations measured in brain homogenate, the blood plasma and RBC membranes. Blood concentrations can be used to estimate imipramine concentrations in the brain.