This chapter examines the use of ecquis in Roman comedy, especially in Plautus. Although formally belonging to the class of adjectives, pronouns or adverbs, the interrogative markers in ec-, introducing independent as well as subordinate clauses, function as particles introducing “total” questions. The ambiguity needs to be clarified by taking into account the fact that the second constituent qu- plays the role of an indefinite, not of an interrogative element, and that its value tends to fade leaving the prefix ec- as the main semantic determinant of the term. In this respect, it is useful to compare numquis, which, unlike ecquis, is still rarely used in the early period. The controversial etymology of ec- is discussed in the light of the semantic and pragmatic nuances that are revealed in different contexts in relation to the previous or following utterance. While in most cases ec- confers on the question a character of insistence and urgency, thus producing different effects of rhetorical meanings, the value of the questions introduced by ecquis seems fundamentally neutral; ecquis, therefore, does not per se orient the interrogation either in a positive or in a negative sense.