BACKGROUND: Understanding the cause for platelet refractoriness in a given patient is the critical step in determining the strategy for optimum management. The aim of this study was to establish the causes and frequency of platelet refractoriness as well as the incidence of anti- HLA antibodies and anti-platelet specific antibodies in multiple transfused thrombocytopenic patients. METHODS: Our study was based on 58 patients requiring platelet transfusions on at least three consecutive occasions from September 1997 to December 1997 in our hospital. The platelet refractoriness was defined as 18-24 hour post-transfusion corrected count increment (CCI) of less than 5,000. Enzyme immunosorbent assay (EIA), panel reactive antibody test (PRA) and Modified antigen capture ELISA (MACE) were applied for the detection of alloimmunization. RESULTS: Thirty-nine patients had episodes of refractoriness (67%). In 39 patients, poor response was seen in 38 patients (97%) with presence of non-immune factors known to be associated with platelet refractoriness. The total rate of alloimmunization was 31%, accounting for fourteen patients (24%) who had HLA antibodies, and four patients (7%) who had platelet specific antibodies. No patient had platelet-specific antibodies in addition to HLA antibodies. From our results, alloimmunization has shown a statistically meaningful relationship with CCI and the use of leukoreduction filtered blood components. CONCLUSION: Our data suggest that immune mechanisms are not the predominant cause of platelet refractoriness and HLA antibodies are produced separately with platelet-specific antibodies, as well as more frequently in alloimmunization.