Gastric tolerability, absorption and pharmacological activity of the non-steroidal anti-inflammatory drug 4-biphenylacetic acid (BPAA), as an inclusion complex with beta-cyclodextrin (beta-CyD) or chemically modified beta-CyDs: 2,6-di-O-methyl-beta-CyD (DM-beta-CyD), 2,3,6-tri-O-methyl-beta-CyD (TM-beta-CyD) and 2-hydroxypropyl-beta-CyD (HP-beta-CyD), were investigated in the rat after oral administration. BPAA absorption, determined from area under the plasma concentration-time curve (AUC), was increased by complexation with all beta-CyDs in the following order: DM-beta-CyD > TM-beta-CyD > HP-beta-CyD > beta-CyD. The carrageenan paw oedema test demonstrated a significant increase in anti-inflammatory activity of BPAA and the ED50 values, compared with BPAA alone, were reduced to about a third for the BPAA-DM-beta-CyD complex and halved for the others. BPAA complexed with DM-beta-CyD, HP-beta-CyD or beta-CyD showed better gastric tolerability compared with uncomplexed drug, whereas the BPAA-TM-beta-CyD complex produced marked gastric lesions similar in extent to BPAA alone. TM-beta-CyD (500 mg kg-1) and DM-beta-CyD (1000 mg kg-1) caused gastric erosions 21 h after oral administration. The pharmacokinetic profiles of BPAA-beta-CyD complexes have shown that DM-beta-CyD is the most effective in enhancing the bioavailability of BPAA.