Naturally occurring lithium consists largely of the stable lithium-7 isotope but it contains 7.6% of a second stable isotope, lithium-6. Biological effects of these two isotopes were not identical. When administered in isotopically pure form, the chloride of lithium-6 was more toxic after acute intake than the chloride of pure lithium-7:its LD in Swiss-Webster mice was 13.2 mEq/kg as opposed to 15.9 mEq/kg for the salt of the heavier isotope and 14.9 mEq/kg for that of the natural mixture of the two isotopes. A single injection of one or the other pure isotope in a constant dose, 14.5 mEq/kg led to a 90% mortality in mice given lithium-6 but only 10% in mice given lithium-7. Side effects such as hypoactivity, ataxia, intense perspiration and diarrhea appeared within 10 min after administration of toxic doses of lithium-6 but more gradually after lithium-7. The differences between the isotopes in toxicity and rate of appearance of effects on spontaneous motor activity were significant at the p less than 1% level.