This invention relates to a novel human deoxyribonuclease, referred to as LS-DNase, that is relatively resistant to inhibition by actin, as compared to human DNase I. The invention provides nucleic acid sequences encoding LS-DNase, thereby enabling the production of LS-DNase by recombinant DNA methods in quantities sufficient for clinical use. The invention also relates to pharmaceutical compositions and therapeutic uses of LS-DNase.