To evaluate the efficacy of lithium carbonate in ameliorating leukopenia, 37 patients (3 to 26 years old, mea (less than or equal to 1,000/mm3) over 40% of the time were designated at random on the last day of 82 separate chemotherapy courses to receive lithium or no treatment. Four could not take the drug because of the size of the capsules. There were 39 controls and 39 patients given lithium. Blood levels were maintained at 0.2 to 1.2 mEq/1 (median 0.7). The median drop of WBC in the treated group was 3,400/mm3 with a nadir of 1,800/mm3 vs 5,000 and 1,400, respectively, for the untreated patients (P LESS THAN 0.01). Eight patients (21%) in the lithium-treated group became severly leukopenic (less than or equal to 1,000/mm3) while 14 (36%) in the control group became leukopenic to that extent. Twenty-four patient days were spent with the WBC less than or equal to 1,000/mm3 after lithium and 57 days in the control group. Three patients required admission for 24 hospital days for fever while leukopenic after lithium, whereas seven patients spent 62 days in the hospital in the control group. Lithium reduces the period of leukopenia after chemotherapy during which time the patients may acquire infections.