Stereotactic Body Radiation Therapy (SBRT) is a potent means of systemic cytoreductive therapy for selected patients with metastatic cancer. We here report an interim analysis of a prospective Phase I/II study of SBRT for liver metastases. Eligible patients with liver metastases met these criteria: (1) maximum tumor diameter < 6 cm; (2) < or =3 discrete lesions; (3) treatment planning confirmed > or = 700 cm3 of normal liver receives < or =15 Gy. The gross tumor volume (GTV) was expanded 5-10 mm to yield the planning target volume, which received 60 Gy in 3 fractions of SBRT over 3-14 days in the Phase II component of the trial. As of July, 2006, 36 patients have been enrolled: 18 in Phase I, 18 in Phase II. The median age was 58 years (range 27-91); the M:F ratio was 20:16. The most common primary sites were lung (n = 10), colorectal (n = 9), and breast (n = 4). Among 21 pts with > or = 6 months post-SBRT follow-up (median 19 months, range 6-29), one instance of SBRT-related grade 3 toxicity occurred in subcutaneous tissue superficial to the liver. No grade IV toxicity occurred. For 28 discrete lesions treated (median GTV 14 cm3, range 1-98) the 18 month actuarial local control estimate is 93%. This interim analysis indicates that a very high rate of durable in-field tumor control can be safely achieved with SBRT to 1-3 liver lesions as administered in this protocol, to a prescription dose of 60 Gy in 3 fractions.