Exacerbations of symptoms have been reported in some women with asthma just prior to and during menstruation. We examined changes in airway responsiveness to methacholine during 2 consecutive menstrual cycles in 17 well-controlled asthmatics with a wide range of airway responsiveness. In 10 women with regular natural cycles, measurements were made 1 wk before and 1 wk after the start of menstruation to coincide with the highest and lowest progesterone levels. The mean concentration of methacholine to cause a fall in FEV1 of 20% (PC20) premenstruation was 1.49 mg/ml, which was not significantly different from the mean postmenstruation PC20 of 1.34 mg/ml (p = 0.45). Although there were only 10 subjects, the power was 96%, indicating little likelihood of any difference between the 2 phases. In 7 women taking oral contraceptives, the mean PC20, measured within 1 wk of completing a 21-day course, was 1.19 mg/ml, which was not different from the mean PC20 of 0.97 mg/ml measured after the start of menstruation but before restarting medication (p = 0.17). The power was 98%. In both groups, there was no difference in FEV1 or medication use during the cycle, but symptoms were worse during menstruation. The results suggest that the fluctuations in serum progesterone levels that occur during natural menstrual cycles are insufficient to alter airway responsiveness in an unselected sample of asthmatic women. They also demonstrate that changes in symptoms occur during the cycle both in women with natural cycles and those using contraceptives and that these changes are not related to serum progesterone levels or airway responsiveness.