To evaluate the possibility that healthy offspring of patients with obstructive sleep apnea syndrome (OSAS) may have covert signs of sleep disordered breathing, we compared the respiratory response to inspiratory resistive loads (IRL) in 10 adult offspring of fathers previously diagnosed with OSAS with that of 14 offspring of healthy parents. None of the offspring in either group had any sign of OSAS, and groups were age, weight, and body mass index matched. Both ventilatory response to progressively increasing levels of IRL and the IRL required to produce severe hypopnea (tidal volume [V(T)] < 20% of unloaded magnitude) were determined, during NREM sleep. Offspring of patients with OSAS (OSAS offspring) responded to all levels of IRL with greater decreases in V(T). Their V(T) decreased in the second breath on IRL of 23 cm H2O/l/s by 39 +/- 10%, as compared with a decrease of 19 +/- 4% (mean +/- SD) in the control group (p < 0.05). Severe hypopnea occurred in the OSAS offspring in response to smaller IRL compared to controls (79 +/- 20 and 153 +/- 14 cm H2O/l/s, respectively, p < 0.005). Total upper airway occlusion in response to IRL occurred in three of the OSAS offspring, but in none of the controls. We conclude that apparently healthy offspring of patients with OSAS may inherit subtle defects that reduce their ability to compensate for increased loads and maintain upper airway patency during sleep. We speculate that offspring of OSAS patients with decreased tolerance to IRL may be prone to developing OSAS later on in life.