Blood samples from 60 patients with serologically positive infectious mononucleosis were analyzed on the Coulter S-Plus IV. Hemoglobins and platelet counts were essentially normal, and leukocyte counts were elevated in less than half the cases. Reactive lymphocytes were present on blood smears from all patients. The S-Plus IV automated three-part leukocyte differentials showed significantly lower numbers of lymphocytes and more mononuclears and granulocytes than manual microscopic differentials. On the leukocyte histograms, lymphocyte peaks were consistently wider than normal and asymmetrical. The instrument generated R2 flags on 43 of 60 (72%) of the samples. Using a combination of "R" flags, mononuclear backlighting, and "H" flags, the Coulter S-Plus IV identified 59 of 60 infectious mononucleosis samples as requiring further review.