Surgical resection of lung tissue is employed clinically as a therapy for pulmonary metastases; however, local cancer recurrence is a frequent post-surgical complication. In a variety of small mammals, left pneumonectomy (PNX) initiates rapid compensatory hyperplasia of the remnant lung lobes restoring normal tissue mass, structure and function. Post-PNX compensatory lung growth is known to promote lung tumor formation in carcinogen-treated mice. The present study tests the hypothesis that PNX enhances experimental metastasis to lung. C57B1/6 mice subjected to PNX were given an intravenous injection of B16F10 melanoma cells at various stages of compensatory lung growth. Animals injected with B16F10 cells during the linear phase of the response had 77% to 260% more pulmonary metastases than mice subjected to thoracotomy (P < 0.01). Moreover, measurements of tumor area (mm2) revealed that PNX mice harbored a substantially larger lung tumor burden than control animals. Normalization of the tumor cell inoculum to lung mass yielded similar results. PNX had no effect on growth of sub-cutaneous B16F10 melanoma tumors, suggesting that experimental melanoma metastasis was enhanced by local alterations in the lung microenvironment. These results suggest (1) that PNX is a relevant model in which to investigate mechanisms of local cancer recurrence and, (2) melanoma cell metastatic potential is influenced, at least in part, by local factors modified during post-PNX compensatory lung growth.