Semiautomated agarose electrophoresis and immunofixation performed with Hydrasys-Hyrys (Sebia) were compared with conventional, manually performed methods, including cellulose acetate electrophoresis, immunoelectrophoresis, and immunofixation. Reference intervals for agarose electrophoresis with Hydrasys-Hyrys were determined. Within-run imprecision (CV) for fraction quantitation with the semiautomated system was between 1% (albumin) and 4.5% (beta-globulin). Total imprecision (CV) was between 2.7% (albumin) and 7.3% (beta-globulin). Semiautomated agarose electrophoresis showed linear correlation with cellulose acetate electrophoresis. Thirty-four specimens with monoclonal components were analyzed by manual immunoelectrophoresis and immunofixation and by Hydrasys. In one case, a light-chain disease was missed with Hydrasys when the sample was diluted 1:3 (the routine dilution) but not when the sample was assayed undiluted. In another case, the Hydrasys system revealed a small IgGA monoclonal component in addition to the IgA monoclonal component detected by the manual methods. In the other cases, no differences between the manual methods and the semiautomated method were seen with respect to paraprotein identification.