In order to determine if expression of the cystic fibrosis gene can be detected in heterozygotes, we determined sweat responses induced by local stimulation with cholinergic and beta-adrenergic agents for 20 heterozygotes, 19 age- and sex-matched controls, and five subjects with cystic fibrosis. Active sweat glands were counted and sweat droplets were collected in constant bore capillaries and measured optically. Each subject was tested two to six times. The central finding was that the sweat response of carriers was significantly lower than controls to beta-adrenergic stimulation (p = 0.0013, two-tailed t test; p less than 0.02, Mann-Whitney U), while cystic fibrosis homozygotes did not sweat at all. In contrast, the cholinergic sweat responses did not differ between carriers and controls. For both groups the correlation between cholinergic and beta-adrenergic sweating was positive, but a linear regression of beta-adrenergic sweat responses as a function of cholinergic sweat responses yielded slopes that were significantly different for the two groups. The ratio of beta-adrenergic to cholinergic sweating was plotted for each subject; the mean ratio of the carriers was approximately half of the mean for the controls (p = 0.0002 using t test or p less than 0.002 using the Mann-Whitney U). Our results confirm previous studies and provide new evidence that carriers have, on average, a beta-adrenergically stimulated secretory response that is significantly reduced relative to the control response.