Although premenstrual worsening of asthma is recognized, little is known about the pathophysiology. Monthly variation in endogenous progesterone and β-estradiol may be associated with the etiology of premenstrual asthma (PMA). T lymphocytes play an importanat role in the pathogenesis of asthma. Therefore, to clarify the pathogenesis of PMA, the clinical features and effects of progesterone and β-estradiol on lymphocyte activation were studied. 1) Thirty one asthmatic females of reproductive age were surveyed. Fourteen asthmatics (45%) claimed their asthma symptoms worsened just prior to or during the menses. Comparing asthmatics with and without PMA, the former group showed significantly more severe steroid dependent asthma. 2) Progesterone and β-estradiol suppressed lymphocyte blastogenesis stimulated by phytohemagglutinin (PHA), mite and Candida antigen. There was no significant difference in the suppression rate between asthmatics and normal subjects, or between male and female. These findings suggest that T lymphocytes may be activated by causal allergens when progesterone and β-estradiol levels decrease during the premenstrual period. Activated T lymphocytes may contribute to the pathogenesis of PMA.