Either inhibition or enhancement of the spontaneous lymphoma exhibited by AKR mice was observed after treatment with different dosages of the sulfhydryl inhibitor, sodium iodoacetate. Treatment of the mice at 3 or 6 months of age with five ip injections of 0.10 mg of iodoacetate at 5-day intervals significnatly extended the survival of the animals. A single administration of this dosage elevated the responses of splenic lymphocytes to the T-cell mitogens phytohemagglutinin (PHA) and concanavalin A (Con A), and resulted in higher PHA and Con A response ratios than were noted for age-matched controls. Conversely, groups of 3- or 6-month-old AKR mice, subjected to the same regimen but with 0.01-mg dosages, exhibited an apparent accelerated development of the leukemia and survived for significantly shorter periods. In general, splenic lymphocytes harvested from mice given a single 0.01-mg treatment of iodoacetate were not as reactive as were control cell cultures when exposed to the T-cell mitogens.