The anti-inflammatory and gastric effects of etodolac were compared in the rat with those of seven clinically established nonsteroidal anti-inflammatory drugs. The anti-inflammatory potency of etodolac was found to lie between that of sulindac and piroxicam. Etodolac was 2.8 times more active than sulindac and 2.2 times less active than piroxicam. Compared to phenylbutazone it was 12.5 times more potent. The irritation produced on the gastric mucosa was less than that of sulindac, although this difference did not reach statistical significance. However, etodolac was significantly (p less than 0.05) less irritant than piroxicam. Of the drugs studied, etodolac showed the highest ratio between the irritant ED50 and the dose which inhibited inflammation by 50%. From these results etodolac is predicted to be a potent anti-inflammatory drug with a high gastric tolerance. Clinical trials appear to confirm these predictions.