When rats were exposed to 2 mg I-' ( -640 ppm) of carbon disulfide (CS,) for 4 h, the concentration of free CS, in the red blood cells (RBCs) approached a plateau within 2 h. Free CS, in plasma reached a steady state concentration within 15 min of exposure. More than 90% of the free CS, in blood was found in the RBCs regardless of the length of exposure. I n vitro studies showed that about 90% of the free CS2 partitioned into the RBCs regardless of whether the CS, was added first to the plasma or directly to the RBCs. Hence, it appears that the RBC is the major carrier of CS, in blood. It was found that 98% of the free CS, in red blood cell lysates was associated with hemoglobin. Free CS, in RBCs was readily partitioned into olive oil (RBCs1oil = 1/6), less readily into the plasma (RBCsIplasma = 12/1), and only to a small extent into phosphate buffer (RBCsIbuffer = 3911). The extraction of free CS,-loaded RBCs into albumin solution increased with increasing albumin concentrations. CS, can be extracted with buffer, protein solution, and oil, indicating that CS, in RBCs can be transferred to the medium in which the RBCs contact. It is proposed that RBCs may also play an important role in the transport of CS, from lung to tissues and vice versa. The possible role of RBCs in the transport of other organic solvents in the blood is also discussed.