Although automation has improved the accuracy and precision of blood cell counts and is more rapid and less labor-intensive, cerebrospinal fluid (CSF) samples are still counted manually. We compared the IRIS iQ200 Body Fluids Module (Iris Diagnostics, Chatsworth, CA) and the Beckman-Coulter LH750 (Beckman-Coulter, Brea, CA) with manual counts and evaluated the impact of automation on the laboratory if clinically acceptable performance was to be maintained. Automated counts were compared with manual counts on 313 specimens. Clinical reliability was estimated using the weighted kappa coefficient and the impact of errors discussed in the context of a historic census of 3,653 samples spanning 19 months. Nucleated cell counts had a reliability of 0.73 for the LH750 and 0.84 for the iQ200. However, our results showed unacceptable rates of error at counts less than 200/microL (200 x 106/L) for the LH750 and less than 50/microL (50 x 106/L) for the iQ200, representing 94% and 83% of the census specimens, respectively. If clinical reliability is to be maintained, neither the LH750 nor iQ200 would have a significant impact on improving the efficiency of the laboratory because of the high percentage of low CSF cell counts.