The sweat gland has three distinct cell types: a myoepithelial (ME) cell, a beta-adrenergic-insensitive (beta-I) cell, and a beta-adrenergic-sensitive (beta-S) cell. Using intracellular microelectrodes, we sought to functionally identify the specific cell type(s) affected in cystic fibrosis (CF). We found that in CF secretory coils 1) the ME calls are unaffected, as indicated by normal cell membrane potentials and spontaneous and cholinergically induced depolarizing potentials, 2) the beta-I cells showed normal physiological properties, including a relatively smaller cell membrane potential (approx -25 mV) and a Ba(2+)-inhibitable cholinergic response, and, in contrast, 3) the beta-S cell is abnormal, as shown by the lack of a beta-adrenergically activated cystic fibrosis transmembrane conductance regulator (CFTR) Cl- conductance (GCl). Lack of CFTR GCl in this cell type does not affect either the magnitude of cell membrane potential (approx -56 mV) or the relative cell membrane GCl or the cholinergic response, as compared with that of normal beta-S cells. We conclude that, of the three cell types in secretory coil, only the beta-S cell is specifically affected in the CF secretory tissue of the human sweat gland.