During 6 cycles of treatment of 19 women, the effect of a low-dose biphasic oral contraceptive containing 40 micrograms ethinylestradiol + 25 micrograms desogestrel (7 tablets) and 30 micrograms ethinylestradiol + 125 micrograms desogestrel (15 tablets) on various hormonal parameters and glucose metabolism was compared with the values of the pre- and post-treatment cycle. There was a profound reduction in gonadotropin secretion and ovarian steroid synthesis. The serum levels of testosterone were reduced by 35%, free testosterone by 55%, and DHEA-S by 30%. Cortisol increased by 100%, SHBG by 250%, and TBG by 60%, while FT3 and FT4 were only marginally influenced. Fasting levels of glucose and insulin did not change significantly, but the glucose load revealed a slight impairment of glucose tolerance. Three weeks after termination of pill intake, the various parameters returned to pretreatment levels, except for SHBG and TBG which were still elevated by 20 to 30%. The results demonstrate a marked preponderance of the effect of the estrogen component, a reliable inhibition of ovulation and very good cycle control during treatment with the biphasic formulation.