The binding of ibuprofen to human serum albumin, normal plasma and plasma obtained from rheumatoid arthritic patients was studied using the method of ultracentrifugation. It was found that ibuprofen is more strongly bound to normal plasma than to human serum albumin although this result is probably explained by fatty acid contamination of the human serum albumin. The fraction of ibuprofen not bound to normal plasma rose significantly from a value of 0.0128 at an ibuprofen concentration of 2 mg X l-1 to 0.0155 at a concentration of 50 mg X l-1. Ibuprofen was less strongly bound to rheumatoid plasma than to normal plasma but this difference can be accounted for by the difference in albumin concentration between the two plasmas. It was found that salicylic acid can displace ibuprofen from protein binding sites, in vitro, and that this is the probable cause of the pharmacokinetic interaction between the two drugs.