Abstract The present study was designed to specifically investigate the in vitro effect of levamisole on responding T lymphocytes and/or suppressor monocytes in patients with breast and colorectal cancer. The mean T lymphocyte response to PHA in the presence of irradiated autologous monocytes was significantly depressed as compared to that in the presence of irradiated autologous T cells in 22 patients with breast cancer ( P<0.001) or in 28 patients with colorectal cancer ( P<0.005). The in vitro treatment of responding T lymphocytes with levamisole failed to enhance the T lymphocyte response to phytohemmagglutinin. The treatment of irradiated monocytes with levamisole (1, 10 or 100 μg/ml), on the other hand, variably lessened the suppressor activity in patients with breast and colorectal cancer. The mean PHA response of T lymphocytes in the presence of levamisole-treated monocytes was significantly higher than that in the presence of saline-treated monocytes in these patients ( P<0.025). Reversal effect of levamisole at a low dose level (1 μg/ml) was not significantly different from that at high dose levels (10 or 100 μg/ml). Our data indicate that the enhancement of T lymphocyte response to PHA is secondary to the specific action of levamisole on suppressor monocytes in breast cancer or colorectal cancer patients.