The effect of oral zinc supplementation in patients with cystic fibrosis (CF) was investigated in a placebo-controlled, double-blind, crossover study with each treatment period covering 6 months. CF patients (n = 13, aged 2 years, 3 months to 19 years, 1 month) started with placebo and after 6 months, they received zinc therapy. Another 13 patients (aged 3 years, 5 months to 16 years, 10 months) started in the reverse order. Before zinc supplementation, all CF patients had low plasma levels of zinc which normalized during treatment. This effect was, however, transient. CF patients also had low concentrations of plasma selenium. A small decrease in the number of leukocytes was also noted during zinc therapy. In response to zinc treatment, no changes in the clinical status of the patients were observed either by the investigators or by the patients. Growth velocity was the same during the placebo and zinc treatment periods. No significant changes in lung function occurred in response to either placebo or zinc. It appears that the observed low plasma zinc concentration in CF patients was due to an impaired zinc absorption from the gut which was counteracted by an increased supply of oral zinc. No beneficial effect from zinc supplementation on clinical status, growth velocity, or lung function was found in this study.