Dynamics and pathways of 125I-labeled albumin (RISA) outflow from brain to deep cervical lymph have been studied in anesthetized rabbits between 4 and 25 h after microinjection of 1 microliter RISA into the internal capsule or midbrain. Lymph from the jugular lymph trunks was collected for periods of 2-11 h. RISA was cleared from brain with half-times of disappearance from internal capsule and midbrain of 18.2 and 11.9 h, respectively. RISA was distributed in high concentration to subarachnoid arteries that supplied the tissue injection site; this was consistent with RISA drainage from brain via perivascular spaces. Outflow through lymph rose to a maximum value 15-20 h after tracer injection. Mean recovery of RISA from lymph over the 25-h collection period accounted for 22% of total loss from internal capsule and 18% from midbrain. This result compares with mean recoveries from caudate nucleus and cerebrospinal fluid of 47% and 30%, respectively [M.W.B. Bradbury, H.F. Cserr, and R.J. Westrop, Am. J. Physiol. 240 (Renal Fluid Electrolyte Physiol. 9): F329-F336, 1981]. These are minimal estimates of total outflow to lymph because of the 15- to 20-h delay in RISA passage from brain to lymph.