The in vitro invasion assay showed significantly less invasion of both Mel 290 cells and B16LS9 cells treated with bevacizumab, with 100 μg/mL bevacizumab being more effective than 10 μg/mL. Invasion of Mel290 cells decreased by 56% and 91% optical density (OD) units after treatment with 10 and 100 μg/mL bevacizumab (0.1063 ± 0.0142 and 0.0877 ± 0.0053), respectively, compared with IgG treatment (0.2399 ± 0.0184, P < 0.001). In B16LS9 cells compared with the IgG control (0.3604 ± 0.0198), 10 and 100 μg/mL bevacizumab reduced invasion by 15% and 27% (0.3064 ± 0.0166, 0.2626 ± 0.0112, P < 0.01), respectively. The human uveal melanoma cell line Mel290 was much more sensitive to bevacizumab than was the mouse melanoma cell line B16LS9. The number of hepatic micrometastases in the control group and the 50-μg and 250-μg bevacizumab groups were 194 ± 86, 108 ± 27, and 63 ± 23, respectively. There were significantly fewer micrometastases in our mouse ocular melanoma model after treatment with either 50 or 250 μg bevacizumab, (P = 0.03 and P = 0.01, respectively), compared with the number in the control group. There was a significant decrease in the number of micrometastases in the 250-μg/mL– compared with the 50-μg/mL–treated groups (P = 0.002). In the longitudinal experiment, treatment with 250 μg bevacizumab resulted in control of the number of micrometastases at all intervals (1, 2, 3, 4, and 6 weeks) after inoculation. The treatment effect continued longitudinally, with significantly fewer micrometastases in mice treated with 250 μg/mL bevacizumab than in the control animals at 1, 2, 3, 4, and 6 weeks after inoculation.