In an effort to reduce the level of presensitization in patients on our heart and lung transplant waiting list, ten patients with random panel reactivity above 10% on monthly screening for durations of 2 to 59 months were given low-dose azathioprine (25 to 75 mg/day) for 1 to 22 months. All patients had positive T-cell panel reactivity (10% to 70%) against specific (n = 6), multi-specific (n = 1), or undefined (n = 3) HLA loci, and four additional patients had positive B-cell panel reactivity (5% to 40%). No effect of azathioprine on panel reactivity was seen in four of ten patients (40%), whereas a significant and sustained reduction in panel reactivity occurred in six patients (60%), all within 2 months of commencing azathioprine. All nonresponders had antibodies with class I (A locus) specificity, whereas all six responders had multi-specific or undefined antibody specificities. A formal trial of low-dose azathioprine in presensitized recipients is warranted.