We have evaluated the prototype and production models of the Coulter Counter Model S over an 11-month period. The built-in diluting system had a precision of better than 1 %. The precision and stability of the production instrument were superior to those of our reference methods. Correspondence of the results of the Model S and those of the routine clinical laboratory was excellent over a 6-week period. Elevated white cell counts produced a small positive error in the hemoglobin determination proportional to the number of white blood cells (WBC). The major difficulties in the use of the instrument were specimen interaction (“carryover”), calibration, and quality control. We have investigated these difficulties and found that they produce no serious limitations in the use of the instrument. Our findings suggest that if other instruments achieve the same performance specifications obtainable with ours, the Coulter Counter Model S represents a major advance in medical instrumentation.