Acetone-fixed cryostat sections of 79 breast carcinomas were immunostained with antibodies to basic fibroblast growth factor (bFGF) and urokinase-type plasminogen activator (uPA). Staining intensity was then compared with microvessel density assessed by manually counting vascular spaces highlighted by immunostaining vascular basal lamina (Type IV) collagen. Extensive (2+) bFGF immunoreactivity was present in neoplastic cells of 30 tumors (38%) and in host-derived stromal cells of 29 cases (37%). Disease recurrence correlated with bFGF staining: 0 to 1+ stromal staining, 30% recurred versus 2+ stromal staining, 73% recurred (P = 0.001) (54-mo median follow-up). Neither stromal nor epithelial bFGF staining correlated significantly with microvessel count; however, there was a statistically significant association between stromal cell bFGF staining and uPA staining of peritumor host cells: absent bFGF--0% 2+ uPA versus weak bFGF--9% 2+ uPA versus 2+ bFGF--29% uPA (P = 0.01). We conclude that elevated expression of bFGF in breast carcinomas is associated with aggressive clinical behavior. Its biologic significance, however, appears more closely related to extracellular matrix remodeling than to induction of prominent neovascularization per se.