The transport and metabolism of radiolabeled leukotriene (LT) C₄ in the CNS were investigated after intraventricular injection. Under thiopental (Pentothal) anesthesia, New Zealand white rabbits were injected intracerebroventricularly with 0.2 ml of artificial CSF containing 2.5 μCi of [³H]LTC₄ (36 Ci/mmol), 0.3 μCi of [⁴C]mannitol, and, in some cases, 0.9 mg of probenecid, 1.8 mg of cysteine, 1.4 μg of unlabeled LTC₄, or 2 mg of tolazoline HCl. After 2 h, the conscious rabbits were killed, and the quantity and nature of the ³H and ¹⁴C were determined in CSF, choroid plexus, and brain. The [³H]LTC₄ recovered in CSF and brain was not extensively metabolized, as >70% of the ³H remained [³H]LTC₄, although some spontaneous conversion to 11‐trans‐[³H]LTC₄ occurred. Oxidized forms of [³H]LTC₄, [³H]LTD₄, and [³H]LTE₄ did not exceed 18% in CSF and brain. After intraventricular injection of [³H]LTC₄, ³H was transferred from the CSF to blood by a probenecidsensitive, but tolazoline‐insensitive, transport system in the CNS much more rapidly than mannitol. Cysteine decreased the retention of [³H]LTC₄ in brain. These results are consistent with previous in vitro observations that [³H]LTC₄ is transferred from CSF into blood by an efficient transport system for LTC₄ in choroid plexus.