The plasminogen activators, tissue type and urokinase type (tPA and uPA, respectively), have been identified in various malignancies and have been implicated in both local growth and metastatic spread. To characterize plasminogen activator expression more fully in human basal cell carcinoma, the localization of uPA and tPA mRNAs was evaluated by in situ hybridization. Nodular basal cell carcinomas demonstrated uPA expression in most cases, whereas the non-nodular subtypes were negative. Message for uPA was identified within tumour islands (11112 cases), scattered fibroblast-like stromal cells (6112 cases), and the basal layer of the overlying epidermis (10112 cases). In addition, signal for uPA was elevated and pronounced in areas where the epidermis merged into invasive basal cell carcinoma in the superficial papillary dermis in some cases. Message for uPA was often associated with ulceration or erosion of the overlying epithelium. Expression of tPA was noted in the epidermis (3112 cases) and in tumour cells (4112 cases), but tended to be focal and sparse. These results suggest that complex interactions involving uPA expression occur between the tumour, the stroma, and the overlying epidermis. Both the stroma and the epidermis may contribute to local spread of the tumour through production of uPA and consequent plasmin-mediated activation of collagenases and metalloproteinases.