Automated differential counts produced by the Coulter S-Plus IV (S + 4) and the Technicon H-1 (H-1) were compared with routine and reference manual differentials with the use of samples from the adult emergency room (ER) and the neonatal intensive care unit (NICU), populations in which rapid reporting of laboratory results is considered important. Error rates for routine technologists were 9.3% in the ER and 15.3% in the NICU. Error rates for the two instruments were higher than those for technologists with samples from the ER but could be reduced to 4-5% if instrument flags and additional criteria were used to signal the need for a conventional differential. Instrument error rates were higher yet with NICU samples, and specificity was very low (10% for each device). There were small differences between the instruments in detection of immature neutrophils, but flags from the H-1 were more specific (except for detection of nucleated red blood cells in samples from the ER). If either instrument were used in an adult ER and flags and additional criteria were used to signal the need for conventional differentials, 64-75% fewer manual counts would be performed with no decrease in accuracy and a considerable improvement in turnaround time.