A high unit dose (15 grain/975 mg) enteric coated aspirin preparation was studied in normal individuals and patients with arthritis to determine how readily well tolerated, therapeutic (150-300 micrograms/ml) salicylate (SA) levels could be achieved using a twice daily dosing regimen. Of 36 participants enrolled, 33 (92%) achieved this goal (mean SA = 224 micrograms/ml), while in the remaining 3 an initially toxic level fell below the therapeutic range after reducing the dose by one tablet/day. Although the relationship between dose (mg/kg) and steady state SA levels was roughly linear (r = 0.74), in some subjects there was a striking incremental change in the SA level when the dose was adjusted. Over 90% of subjects taking a starting dose between 45-60 mg/kg/day achieved a therapeutic level. Thus, antiinflammatory therapy using 15 grain/975 mg enteric coated aspirin given twice daily appears to be feasible.