The absorption of oral methotrexate (MTX) has been studied in 124 children with acute lymphoblastic leukemia (ALL). Blood levels of MTX were very variable and unpredictable. There was a 20-fold difference between the highest and lowest peak level achieved. Division into two groups has shown that those children who absorb MTX slowly have a worse disease-free survival. It is possible that MTX damages the intestinal mucosa and causes a malabsorption of itself in some children. It is suggested that future protocols for the treatment of ALL should include pharmacokinetic studies, which may help to explain the unexpected relapses of good prognosis patients and lead to the development of more effective treatment.