The human cell line NHIK 3025 has a cytoplasmic dexamethasone receptor. When these cells are exposed to glucocorticoids, the cell cycle time is prolonged. The structural requirements for this effect were investigated by measuring cell number after 4 days exposure to different glucocorticoid analogues at concentrations of 10(-6) M and 10(-7) M. Growth inhibition at 10(-7) M required the 4-5 double bond, the 3,20 ketone--and the 11 beta, 17 alpha and 21 hydroxygroups of the glucocorticoid structure, e.g. cortisol, dexamethasone and prednisolone. Other synthetic glucocorticoids like bimetrazol and triamcinolone acetonide were also active at this dose whereas corticosterone, lacking the 17 alpha hydroxygroup, was only active at 10(-6) M. The effect was steroid specific and could be inhibited by anti-cortisol antiserum or by glucocorticoid antagonists.