2. In investigating whether the therapeutic effect of cortisone is due to its inhibitory action on connective tissue rather than to a specific hormonal regulatory effect, aminopterin, which has a specific inhibitory effect on connective tissue proliferation, was given to 7 patients with rheumatoid arthritis and one with acute rheumatic fever. The daily dose was from 1 to 2 mg. and the total dose varied from 6 to 40 mg., given over from 6 to 21 days. In all but one patient who showed no improvement in 6 days, when treatment was stopped, there was marked clinical improvement. On withdrawal of the drug the remissions persisted for up to 6 weeks, when, relapse occurred, but further relief was obtained when the drug was given again. Toxic symptoms, especially buccal ulceration, occurred in most patients, their appearance commonly coinciding with the onset of clinical improvement.

After treatment there was no significant change in the y-globulin level of the blood, in the blood sedimentation rate or in the white cell or eosinophil count. There had been marked improvement in a co-existing psoriasis in one of the patients, so 5 other cases of rheumatoid arthritis with psoriasis and 3 cases of uncomplicated psoriasis were treated with daily doses of from 1.5 to 2.0 mg. aminopterin, and total doses of from 19 to 120 mg. In all there was improvement in the skin condition, starting between the 5th and 10th days; remissions of from 3 weeks to 2 months were maintained after withdrawal of the drag.. Further courses produced similar improvement and one patient was maintained in remission for. 5 months on a daily dose of 0.75 mg. The rheumatic symptoms improved also except when of very long standing. Toxic effects, when present, disappeared a few days after withdrawal of. the drug, though the remission might continue for some weeks. The significance of the findings is discussed, and it is suggested that not only aminopterin, which experiment has shown to act by inhibiting tissue activity and not by stimulating the adrenal cortex, but also therapeutic agents active for rheumatic diseases, such as cortisone, adrenocorticotropic hormone, salicylates and X-rays, may act through a similar inhibition of connective tissue reactivity. Aminopterin inhibits epithelial tissues also.-L. Wills.