High-dose steroids are known to be potent modulators of the immune response. We accordingly investigated the effect of therapeutic doses of 17 beta-oestradiol (E2) on cellular immune responses in post-menopausal women. Fifteen (15) healthy women who had undergone a natural menopause were treated with E2 in the form of 100 mg estraderm patches applied twice weekly for 3 out of every 4 weeks over a 3-month period, followed by combined oestrogen and progestogen formulations as long-term therapy. Blood samples were taken on two occasions prior to treatment and at weeks 1, 3, 4, 7, 9, 12 and 24 after commencing therapy. Lymphocyte subsets (CD2, CD4, CD8, CD19, HLA-DR and NK) were studied in each blood sample using a monoclonal antibody kit and a two-colour fluorescence flow-cytometer. One-way mixed lymphocyte reactions (MLRs) were performed using the same stimulator throughout. Delayed hypersensitivity skin tests (DHTs) were carried out twice before treatment and at weeks 3, 4, 12 and 24 using Multitest 7-antigen kits (Institut Mérieux). Lymphocyte subsets did not change significantly with treatment, but both the MLRs and the DHTs were significantly depressed, maximally so by the third week of treatment. We conclude that therapeutic doses of E2 modulate certain immune responses. The significance of this is discussed in the light of the increasing use of long-term oestrogen replacement therapy.