We measured 6-mercaptopurine levels in the cerebrospinal fluid and plasma of 15 children undergoing treatment for acute leukemia. Plasma and cerebrospinal fluid samples obtained by lumbar puncture were collected before, during, and after cranial irradiation in order to evaluate a possible change in blood-brain barrier permeability to orally administered 6-mercaptopurine. Considerable interpatient variability has been observed in both plasma and cerebrospinal fluid 6-mercaptopurine levels. No statistical differences in the 6-mercaptopurine cerebrospinal fluid levels under the three different conditions could be detected. Our data suggest that cranial irradiation does not significantly influence the cerebrospinal fluid levels.