Monoclonal antibodies, raised against purified human milk fat globule membranes, were applied to human tissue and the corresponding antigenic determinants detected by an immunoperoxidase method. In human breast tissue, the presence of antigenic determinants was characterized by considerable heterogeneity although it is confined to epithelial cells and cannot be detected in non-epithelial areas. The effect of fixation and paraffin embedding on the reaction pattern was evaluated on tissue from 25 primary breast carcinomas. For each tumor, both frozen, acetone fixed and fixed, paraffin embedded tissue was available. Four of the eight applied antibodies could detect fewer positive cells in formalin-fixed tissue as compared to frozen, acetone-fixed tissue from the same tumor. The positive peroxidase reaction was better preserved after fixation in Lillie's solution. Treatment of formalin-fixed tissue with pronase did not give a better effect. Antibodies with preserved positive reaction in formalin-fixed breast tissue were applied to a range of epithelial and non-epithelial human malignant tumors of varying origin. A heterogeneous positive reaction could be detected in the majority of tumors derived from epithelial cells, but not in non-epithelial tumors.