We studied the effect of indomethacin on intradermal skin testing and antibody responses in humans. Since we and others have shown that prostaglandins are suppressor cell mediators, it was probable that in vivo inhibition of prostaglandin synthesis might enhance the humoral and/or cellular immune response. Administration of indomethacin (Indocin) in a dosage of 100 mg/day to 15 normal men and women resulted in a significantly increased antibody titer to A-Victoria (P less than 0.025) as compared with age- and sex-matched controls. There was no difference in titer to A-New Jersey. Since 90% of the subjects had antibody titers to A-Victoria before inoculation, whereas none had detectable titers to A-New Jersey, we interpret this data as suggesting that indomethacin enhances the secondary but not the primary humoral immune response. Indomethacin administration did not alter the intradermal skin test responses.