A number of antibiotics, most of which specifically inhibit protein synthesis by interacting with the 50S ribosome subunit, were used to study polysome metabolism in vivo. The antibiotics affected polysomes in two ways: (i) by allowing extensive breakdown of polysomes, or (ii) by stabilizing polysomes, even in the presence of the antibiotics of the first group. The results indicate that the effect of these antibiotics on polysome stability in vivo can, in many cases, be correlated to their in vitro mode of action.