An experimental comparative study was conducted on 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (piroxicam), indometacin and phenylbutazone for antiinflammatory and analgesic effects and for gastric and intestinal damage. In some of the experimental models used a comparison was made between oral and rectal piroxicam. The upshot was that: the antiinflammatory activity of piroxicam on carrageenin edema in the rat is equivalent by oral and by rectal route, about twice that of indometacin and 20 times that of phenylbutazone. The inhibition of leucocyte migration in the rat was equal to that of indometacin and 20 times that of phenylbutazone. The analgesic activity of piroxicam (phenylquinone writhings in the mouse) was about 1/4 that of indometacin and 70 times that of phenylbutazone. The ulcerogenic effect of piroxicam on the stomach of the rat was about 1/3 that of indometacin and 5 times greater than that of phenylbutazone. Rectal administration halves the ulcerogenic effect of oral piroxicam. The intestinal perforating effect of piroxicam in the rat is about 1/6 that of indometacin and about 15 times that of phenylbutazone. The therapeutic index, i.e., the ratio of antiinflammatory potency to gastrointestinal damage, proved to be appreciably higher for piroxicam than for the two reference standards. Rectal administration carries an even higher therapeutic index and so appears to be a potentially valuable alternative route in clinical practice.