The clinical and metabolic effects of equine estrogen and dydrogesterone combined therapy were investigated in twenty healthy women aged 45 to 59 years with menopausal complaints. Equine estrogens (0.625 mg per day) were given for 2 months, then dydrogesterone (20 mg daily) was cyclically added for 12 days per month, during an additional period of 6 months. The combination was very efficacious in reducing complaints, with a limited number of side effects. Blood pressure, body weight and cervical smears were unaffected. No influence on glucose tolerance, liver or blood coagulation parameters was seen. A VLDL cholesterol decrease of 41% and an increase in apo AI concentrations of 41% was observed. Total, HDL and LDL cholesterol remained almost unaltered, as well as the total:HDL cholesterol ratio. We conclude that the use of the equine estrogen-dydrogesterone combination provides an efficacious, acceptable and probably safe therapy for menopausal complaints.