Cigarette smokers with asthma are insensitive to the therapeutic effects of corticosteroids. It is not known whether this insensitivity to corticosteroids in smokers affects tissue sites beyond the airways. A total of 75 asthmatic subjects (39 smokers) and 78 healthy controls (30 smokers) were recruited to an observational study. The cutaneous and peripheral blood lymphocyte responses to corticosteroids were measured. The cutaneous vasoconstrictor response to topical beclometasone was measured by applying different concentrations of beclometasone solutions to the skin in a random double-blind manner. The degree of blanching at each concentration was graded after 18 h. The sensitivity of peripheral blood lymphocytes to corticosteroids was assessed by measuring the suppressive effect of dexamethasone on lymphocyte proliferation stimulated by phytohaemagglutinin (PHA). Total mean+/-sd cutaneous vasoconstrictor response score to beclometasone was reduced in smokers with asthma to 5.39+/-3.58 versus 7.26+/-3.05 in never-smokers with asthma; and in all smokers to 6.47+/-3.33 versus 7.86+/-2.81 in all never-smokers. The sensitivity to corticosteroids of lymphocytes stimulated by PHA was similar between groups. In conclusion, smokers with asthma have an impaired cutaneous vasoconstrictor response to topical corticosteroids compared with never-smokers with asthma. This finding suggests that the insensitivity to corticosteroids in smokers with asthma affects tissue sites other than the airways.