Host defense mechanisms in transfusion-dependent non-splenectomized patients with ~3-thalassemia were studied. Polymorphonuclear leukocytes (PMNLs) of non-splenectomized patients responded poorly to zymosan generated chemotactic factors. Chemotactic indices were 22.1/am -+ 2.8 (mean -+ S.D.) using zymosan activated serum (ZAS) as the attractant in comparison to 20.4/am + 2.6 when fresh untreated serum was used. In contrast, chemotactic indices of normal PMNLs increased from 21.1/am to 33.6/am -+ 3.1 in response to ZAS. Normal PMNL responses to a mixture of normal ZAS and thalassemic serum were inhibited; the mean chemotactic index was 18.1 pm + 5.1 with use of ZAS alone. Splenectomy temporarily reverses these alterations. Adherence to nylon wool of PMNLs suspended in fresh thalassemic serum prior to splenectomy was 3.1% -+ 1.1 (mean -+ S.D.); 20 days after splenectomy adherence increased to 14.0% -+ 2.8 (P = 0.0001) and remained at this level for 90 days. At 120 and 150 days after splenectomy adherence decreased to 1.5% -+ 0.8 and 1.0% + 0.85 respectively. Splenectomy also transiently abrogated the failure of zymosan to generate chemotactic factors in thalassemic serum.