For purposes of mass drug screening, the procedure for analysis of meconium for drugs was modified into a one-step extraction and analysis by enzyme immunoassay. The accuracy of this modified method was tested by comparing the results of simultaneous analysis of 61 meconium samples for cocaine opiate and cannabinoid metabolites by both the original and the modified methods. In 61 samples analyzed, opiate was detected in 8 (13%) samples by the original method and in 9 (15%) by the modified method; cocaine was detected in 39 (64%) samples by the original method and in 39 (64%) by the modified method. The concordance between the negative and positive results of the modified versus the original methods was 98% and 100%, respectively, for opiate and 95% and 98%, respectively, for cocaine. Only one sample was positive for cannabinoid. Thus a comparison of positive results for cannabinoid was not done; however, all the negative results obtained by the modified method were confirmed by the original method. The clinical experience of mass meconium drug testing using the modified method in 1991 is also reported. In four centers tested (total tests = 4409), the prevalence of presence of drug was consistent with the high- or low-risk status of the population. This simplified, rapid procedure can be performed in most clinical laboratories. This adaptation has made the meconium drug test feasible for large-scale clinical and research use.