Analytical methods were evaluated for measuring cocaine (CO), benzoylecgonine (BE), and ecgonine methyl ester (EME) in urine and methanolic extracts from meconium and diapers by isotope dilution gas chromatography/mass spectrometry (GC/MS). Volatile derivatives of the extracted drugs were generated before GC/MS analysis. Methanolic extracts from meconium and diapers were reconstituted in drug-free urine and treated as above. The limit of detection for the GC/MS method was calculated to be approximately 11 ng per mL. Within-run coefficients of variation (CVs) for urinary CO, BE, and EME were 5.7, 5.3, and 11.4 percent, respectively (N = 10); corresponding CVs for meconium 6.4, 10.7, and 21.9 percent (N = 8). Quantitative results were linear from 25 to 10,000 ng per g of meconium and 25 to 5,000 ng per mL of urine. Day-to-day precision varied from eight percent (CV) for BE in refrigerated or frozen urine to 34 percent for EME in refrigerated meconium. Recoveries of CO, BE, and EME from urine were 63, 19, and 42 percent, respectively; corresponding recoveries from meconium were 64, 21, and 25 percent. Cocaine and metabolites were extracted from wet but meconium-free diapers into methanol, which was evaporated before reconstituting in drug-free urine and extraction on a solid phase column. The CO, BE, and EME were detected in previously drug-free meconium after portions were deposited in a diaper which was wet with drug-positive urine. Unless precautions are taken to prevent extracorporeal contamination of meconium with urine, concentrations of CO and metabolites in meconium may be substantially augmented by contamination with urine. Analysis by GC/MS of CO and metabolites extracted from diapers provides an attractive alternative to collection of urine, which is difficult and may cause discomfort for the neonate.