Activated platelets release angiogenic growth factors and have therefore been proposed to contribute to tumor angiogenesis within a potentially prothrombotic tumor microcirculation. The aim of the study was to investigate interactions of platelets with the angiogenic microvascular endothelium of highly vascularized solid tumors during growth and in response to endothelial stimulation in comparison with normal subcutaneous tissue. Experiments were performed in the dorsal skinfold chamber preparation of C57BL/6J mice bearing the Lewis lung carcinoma (LLC-1) or methylcholanthrene-induced fibrosarcoma (BFS-1). Fluorescently labeled rolling and adherent platelets, red blood cell velocity, and vessel diameters were assessed by intravital fluorescence microscopy on days 1, 3, 8, and 14 after tumor cell implantation. Slightly elevated numbers of rolling platelets were observed in the early stages of tumor angiogenesis at day 1 (control, 1.7 +/- 0.6; LLC-1, 3.4 +/- 1.8; BFS-1, 3.0 +/- 0.7 [1/mm/s], P <.05) and day 3 (control, 1.6 +/- 0.6; LLC-1, 4.1 +/- 1.7, P <.05; BFS-1, 2.3 +/- 0.5 [1/mm/s]) after tumor cell implantation. Endothelial stimulation with calcium ionophore A23187 at day 14 after tumor cell implantation resulted in a minor increase to 2.1 +/- 0.4 (LLC-1) and 1.8 +/- 0.8 (BFS-1) rolling platelets (1/mm/s) in tumor microvessels compared with 4.9 +/- 0.9 in controls (P <.05). Platelet adherence was not observed. We therefore conclude that in the 2 experimental tumors under study, (1) slightly increased platelet rolling is a transient phenomenon after tumor cell implantation, and (2) platelet-endothelial interaction in response to endothelial stimulation is reduced in tumor microvessels.