Many drugs are bound to plasma proteins (PR) and/or to erythrocytes (RBC). The RBC count may change due to physiologic factors such as exposure to high altitude, or pathologic conditions such as anemia or as consequence of cancer treatment. The purpose of the investigation was to study the influence of 1) drug concentration, and 2) number of RBC on erythrocyte uptake or binding using meperidine as a model drug (M). Human RBC concentrated blood was used and blood chemistry determined. Using human plasma (P) dilutions were made containing 9.9, 7.62, 5.87 and 4.11 million RBC mm3. The whole blood (WB) samples were spiked with M to result in 10, 25, 50, or 75 micrograms/ml. Increasing concentrations of M within each group of same RBC count did not influence percentage of erythrocyte uptake/binding. Increase in RBC count from 4.11 to 9.9 million/mm3 resulted in significant increase in erythrocyte uptake from 77.1% to 94.7% and increase in PR binding from 37.2% to 87.4%.