The efficacy and safety of short-term supplemental peripheral hyperalimentation (PH) was evaluated in 15 hospitalized cystic fibrosis (CF) patients who exhibited varying degrees of pulmonary disease severity and nutritional impairment. An average of 1000 supplemental calories/day were administered intravenously for a 2- to 3-week period to patients being treated with parenteral antibiotics for exacerbation of their pulmonary disease. Eleven of 15 patients responded with a weight gain of greater than 2.0 kg and showed continued weight gain and stabilized pulmonary status for the 6- to 12-month follow-up period; two patients showed dramatic reversal of poor weight gain and growth following PH. Total calorie intake (oral + PH) equaled 141 +/- 40% of the recommended dietary allowances (RDA) in responders, with 45 +/- 12% RDA contributed by PH, in contrast to 68 +/- 20% of the RDA for total calories with 31 +/- 13% supplied using PH achieved in the nonresponders. Linoleic acid deficiency was documented in these patients (linoleic acid level as a percent of total fatty acid = 21.9% +/- 1.41 SEM vs 31.8% +/- 1.16 SEM in normal controls), and all seven patients achieved normalization of linoleic acid level after PH. Prior assessment of nutritional status (anthropometric measurements) or of severity of pulmonary disease (NIH clinical score) did not allow prediction of response to PH. No complications resulted from administration of PH to these hospitalized CF patients.