Circulating autoantibodies to human fetal pituitary cells were detected in 13 out of 51 patients who underwent transsphenoidal microsurgery for Cushing's disease. The absence of Fc receptors on human fetal pituitary corticotropin-producing cells allowed the detection of antibodies to these cells. In all the 13 patients, the antibodies were present before surgery, and 10 of them showed clinical and/or biochemical signs of incomplete cure of Cushing's disease after surgery. Only 3 out of 27 patients with a favourable outcome were antibody-positive. In all the antibody-positive patients, the antibodies were directed to corticotropin-producing cells and in 8 patients also to luteinising hormone or human growth hormone producing cells. A non-antigen-specific adherence of antibodies to Fc-receptors on corticotropin-cells was excluded by unchanged binding after preincubation of sections with purified rabbit Fc or Fc aggregates. The presence of pituitary corticotropin-cell antibodies in patients with Cushing's disease is associated with an unsuccessful outcome after transsphenoidal selective adenectomy.