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The paper presents the interrogative and negative constructions in Israeli Sign Language (ISL). Both manual and nonmanual components of these constructions are described, revealing a complex and rich system. In addition to the basic lexical terms, ISL uses various morphological devices to expand its basic question and negation vocabulary, such as compounding and suffixation. The nonmanual component consists of specific facial expressions, head and body posture, and mouthing. The use of mouthing is especially interesting, as ISL seems to use it extensively, both as a word formation device and as a grammatical marker for negation. Interrogative and negative constructions interact in with other grammatical categories in the language; i.e., the distribution of various negation words is determined by the lexical category of the negated word. Thus, the distribution of negation words provides evidence for the existence of Nouns, Verbs and Adjectives as formal categories in the language. Finally, a diachronic comparison between present day ISL and earlier stages of the language reveals interesting traits in the development of these systems.