An extensive study was undertaken to compare five methods of blood smear preparation. Three mechanical devices for preparing blood smears were compared to the traditional coverslip and manual wedge methods. A series of five slides was prepared from each sample of blood. One hundred-cell leukocyte differential counts, red cell morphology, and platelet distribution were compared. Differential counts along the axis and margins of each slide failed to reveal any significant distribution difference by method. On the other hand, there were a significantly fewer neutrophils as well as higher lymphocyte counts on the two spinner preparations. Subsequent analysis suggested that spinner preparations create more smudge cells in smears of normal and granulocytic leukemia patients, and significantly fewer smudge cells in smears of lymphocytic leukemia patients. Both spinner methods produced significant increases in erythrocytic target cells, spherocytes, and cells with shifted pallor; and significantly fewer burr cells and ovalocytes, as compared to the reference methods. The mechanical wedge device was most similar to both reference methods. Of the two reference methods, the cumbersome coverslip preparation apparently offers no practical advantage over wedge methods.