Sixty-three patients have provided evidence that platelets are highly immunogenic even in recipients of potentially immunosuppressive therapy for malignant diseases. Approximately 70 per cent of patients who receive repeated transfusions of platelets from random donors over a prolonged period can be expected to develop lymphocytotoxic antibodies. Antibodies became detectable in one patient ten days after his first exposure to HLA antigens in the form of platelet concentrates, and as early as four days in two patients with prior exposure to HLA antigens. In the most heavily immunized patients, the presence of antibody correlated with poor increments of platelets after transfusion. Patients with prior exposure to HLA antigens are more likely to have antibodies resulting in poor platelet survival. On the other hand, 30 per cent of recipients of repeated platelet transfusions show no tendency to form cytotoxic antibodies.