Extrapulmonary beta 2-adrenoceptor mediated responses to salbutamol were evaluated in 9 healthy female subjects during the follicular (day 2-4, Visit 1) and luteal (day 21-23, Visit 2) phases of the menstrual cycle, and were compared with those of 9 age-matched male controls. At each visit, salbutamol was given by intravenous infusion for 30 minutes at a dose of 0.2 mg.kg-1.min-1. Plasma salbutamol concentration and responses in heart rate (HR), finger tremor (Tr), Q-T interval (Q-Tc), serum potassium (K), serum insulin (Ins) and serum glucose (Glu) were measured at baseline and at 10, 20 and 30 minutes after commencing the infusion. Comparisons were made between sexes and between visits for peak responses calculated as percentage change from baseline. Mean plasma salbutamol concentration (ng.ml-1) were not significantly different between males and females on Visit 1: 6.9 (95% CI 6.01, 7.82) vs 7.3 (95% CI 6.4, 8.3), or on Visit 2: 6.9 (95% CI 6.0, 7.8) vs 7.2 (95% CI 6.3, 8.1). On Visit 1, significantly greater responses were demonstrated in females, compared with males for K (as mean difference): 6 (95% CI 1, 11)%, Tr: 17 (95% CI 1, 33)%, Q-Tc: 8 (95% CI 2, 14)% and Ins: 276 (95% CI 71, 481)%. In addition, a significantly greater response was demonstrated in females on Visit 1 compared with males on Visit 2 for HR (as mean difference): 32 (95% CI 1, 63)%, and for Ins: 262 (95% CI 57, 467)%. Thus, despite no difference in plasma salbutamol concentrations, female subjects exhibited greater responsiveness to salbutamol compared with males during the follicular phase of the menstrual cycle. This suggests that in vivo, females have enhanced sensitivity of extrapulmonary beta 2-adrenoceptors.