In a double-blind clinical trial with 31 premenopausal women suffering from climacteric symptoms, 16 (group A) were treated with an estrone (sodium estrone sulfate 1.5 mg)-norethisterone (5 mg) combination, and 15 (group B) were treated with an estrone-megestrol acetate (5 mg) combination. These treatments effectively alleviated climacteric symptoms without causing any bleeding disorders or pathological changes in the cytology of the uterine cervix or endometrium. In groups A and B, respectively, postovulatory progesterone concentrations above 5 nmoles/liter were found in six and five patients before, in five and seven patients during, and in two and four patients after the treatments. Serum levels of luteinizing and follicle-stimulating hormones decreased significantly and testosterone decreased slightly during both treatments. Serum cholesterol (P less than .01) and high-density lipoprotein cholesterol(P less than .001) in group A decreased during the treatment; only the high-density lipoprotein cholesterol values (P less than .05) decreased in group B. Because of the minor endocrine and metabolic changes without any significant difference between the progestins, both norethisterone acetate and megestrol acetate seem to be suitable for estrogen-progestin combinations aimed at alleviating climacteric symptoms.