The detection of hydrocodone in meconium samples is reported for the first time. Hydrocodone, a semisynthetic antitussive and analgesic, is often prescribed as a painkiller following minor surgery or dental work. It also cross-reacts in enzyme and fluorescence polarization immunoassay opiate systems. In two cases recently received by our laboratory, hydrocodone was detected following a positive opiate immunoassay screening result. The meconium samples were not hydrolyzed because previous work in our laboratory showed that greater than 70% of morphine in meconium is not glucuronide bound. The confirmatory procedures showed that, in case No. 1, codeine was also detected but at a much lower concentration than the hydrocodone. In case No. 2, morphine was detected but, again, at a much lower concentration than the hydrocodone. Even though in both samples another opiate was also detected, the possibility still remains that a positive opiate test result may be reported by screen-only laboratories based solely on the presence of hydrocodone. We present a novel extraction method and a gas chromatographic-mass spectrometric confirmatory procedure for the determination of hydrocodone and hydromorphone in meconium. © 1995 Oxford University Press.