Trisomy 21 produces excess sensibility to methotrexate (dihydrofolate reductase inhibitor). A trial of medication with folinic acid (5-formyl-tetrahydrofolate) was realized on 39 trisomic 21 patients. 30 of them were affected by severe infantile psychosis and the other 9 were affected by a severe Alzheimer-like regression. On 69 assays, 37 were favorable and 32 were null. A dose/effect correlation was highly significant. It is proposed that a systematic investigation of the effects of folinic acid (associated or not with monocarbon precursors) be studied in cases of trisomy 21 complicated by precocious psychosis or severe secondary regression.