In view of the fact that glucocorticoids have an immunosuppressive effect and the fact that interleukin-10 (IL-10) is inhibitory to T helper cell function, we have now investigated the effect of hydrocortisone on plasma IL-10 concentrations. Seven normal subjects were injected with 100 mg hydrocortisone intravenously between 8 and 9:00 a.m. Sequential blood samples were obtained prior to and 1,2,4,8 and 24 h after the injection. Plasma IL-10 concentrations increased significantly and consistently following the injection in all subjects. The peak increase of IL-70 occurred at 4 h and the restoration to baseline by 8 h. The sequential values were (mean+/-SD):, 3.0 +/- 1.3 pg/ml at 2 h, 9 +/- 4.2 pg/ml at 4 h, 3.7 +/- 1.8 pg/ml at 8 h and 3.7 +/- 1.4 pg/ml at 24 h. The magnitude of increase was 436% of the basal at peak effect. This effect of hydrocortisone (and possibly other glucocorticoids) may contribute to the immunosuppressive effect of this drug. IL-10 may also be potentially useful in the assessment of Cushing's Syndrome as a marker of end organ effect of glucocorticoids.