Cystic fibrosis (CF) is characterized by high sweat sodium and chloride concentrations. CF patients have long been assumed to be at risk for heat illness, but there has been no quantitative documentation that CF patients actually have a greater loss of sodium and chloride than normals when under environmental stress. We compared thermoregulatory responses of eight CF patients with five normal controls during 90-min exposures to exercise and heat stress. Both groups reached similar peak rectal temperatures and peak heart rates; they had similar sweat volumes and rates. CF patients showed the normal rise in renin and aldosterone and the normal fall in urine sodium excretion; however, CF patients lost significantly more sodium (48.8 ± 23.4 mEq/liter/m2versus20.2 ± 11.2 mEq/liter/m2) and chloride (46.6 ± 21.6 mEq/liter/m2versus18.5 ± 11.3 mEq/liter/m2) per unit of surface area than the controls. Serum sodium and chloride concentrations fell in the CF patients but not in the normals. After exercise/heat stress, CF serum chloride was significantly less than normals' (99 ± 3 mEq/literversus104 ± 1 mEq/liter,PCF patients have normal temperature, heart rate, hormonal, and renal responses to exercise and heat stress, yet still lose significantly more sodium and chloride than normal. These losses are reflected in part in lower serum concentrations of these ions. There may be important effects of these losses on respiratory tract secretions.