N epsilon (gamma-glutamyl) lysine isopeptide bonds were detected in situ in histological sections from benign and malignant human breast tissue using the monoclonal antibody (MAb) 81D1c2. On cryostat sections of fresh-frozen mammary tissue post-fixed in acetone, or on paraffin sections also from mammary tissue fixed in Bouin's solution, the MAb reacted preferentially with glandular epithelial cells and staining was restricted to the nuclei. In 41 out of 44 benign lesions examined, staining was strong or moderate, while in 25 out of 33 malignant lesions no staining was observed. In the 8 remaining lesions of this group, staining was positive but weak. The difference in reactivity of this MAb with the 2 types of lesions is highly significant (p less than 0.0005) according to the chi 2 test.