Nutritional status and chronic pulmonary hyperinflation can alter respiratory muscle function in cystic fibrosis (CF). This study investigated: 1) whether inspiratory muscle function is reduced in children with stable CF in comparison with healthy controls; and 2) the mechanisms leading to inspiratory muscle weakness, which probably predispose to respiratory muscle fatigue. We determined the tension-time index of the inspiratory muscles (TTMUS) noninvasively at rest in 16 children with mild to moderate CF (mean age, 11 +/- 2 years) and 10 healthy controls (mean age, 11 +/- 2 years). The TTMUS was determined as follows: TTMUS = TI/TTOT.PI/PIMAX, where PI is the mean inspiratory pressure estimated from the measure of mouth occlusion pressure (P0.1), PIMAX is the maximal inspiratory pressure, and TI/TOT is the duty cycle. The results showed similar nutritional status in both groups, as well as mild to moderate airway obstruction, hyperinflation, and trapped gas in the CF group. In this group only, a significant inverse relationship was found between TI/TOT and PI/PIMAX[TITTOT = 0.482 - (0.388PI/PIMAX), r = -0.53; p < 0.05]. These patients also had greater TTMUS (TTMUS = 0.087 +/- 0.030 in CF vs. 0.056 +/- 0.014 in controls, P < 0.01) that increased with decreasing lean body mass (r = -0.70, P < 0.005), with increasing percent predicted functional residual capacity (r = 0.70, P < 0.05), and increasing volumes of trapped gas (r = 0.77, P < 0.01). The multiple linear regression analysis for these factors was significant (R2 = 0.84, P < 0.01); however, the partial regression coefficient was significant only for lean body mass (r2 = 0.60, P < 0.05). Therefore, muscle mass appeared as the strongest determinant of TTMUS in CF. This study used a noninvasive method to assess the inspiratory muscle performance in children with CF. The results suggest impairment in inspiratory muscle function in these children despite good nutritional status and only mild to moderate alteration in pulmonary function tests. In addition, we were able to investigate some of the determinants of inspiratory muscle weakness, namely, muscle mass, hyperinflation, and trapped gas, and found that muscle mass played a predominant role.