Clinical data are now available on the use of recombinant human DNase (rhDNase) in the treatment of CF patients with mild, moderate and severe pulmonary disease. Phase I studies were conducted and indicated the initial safety of rhDNase in humans. In the US phase II study, 181 patients with FVC > or = 40% were randomly allocated to receive rhDNase 0.6, 2.5, 10 mg, or placebo twice daily for 10 days. All three doses of rhDNase significantly improved FEV1 10-14% and FVC 10-12% compared to placebo. There was no significant increase in serious intercurrent events but a slight increase in pharyngitis and voice alteration. A phase II study including 71 patients was carried out in the UK. FEV1 improved by 13% from baseline compared to placebo. There was an improvement in CF-related symptoms and no increase in serious adverse events. The phase III double-blind placebo-controlled study included 968 patients with FVC > or = 40% predicted. These patients were randomized to 2.5 mg rhDNase, once or twice daily, or placebo for 24 weeks. Compared to placebo, rhDNase-treated patients had a relative risk of protocol-defined respiratory tract infection reduced by 22 and 34% and improved FEV1 compared to baseline by 5.8% (p < 0.001) and 5.6% (p < 0.001), respectively, compared to placebo. A double-blind, short-term, placebo-controlled study in severely ill patients, FVC < 40% predicted, showed the drug to be safe but there was no significant improvement in lung function. After a further 6-month open-label treatment, patients showed improvement in FEV1 and FVC.(ABSTRACT TRUNCATED AT 250 WORDS)