Thalidomide and two analogues, EM87 and EM12, inhibited the attachment of tumor cells to concanavalin A coated surfaces only if the drugs were first incubated with hepatic microsomes and cofactors. Most agents which inhibit attachment are demonstrated teratogens. Thalidomide undergoes spontaneous hydrolysis to at least 12 products in saline buffered to a pH of greater than 7. These hydrolysis products did not inhibit attachment nor could they be activated to inhibitory products with hepatic microsomes. Similarly EM12 and EM87 hydrolysis products were neither inhibitory nor substrates for activation. If the three drugs were incubated in buffered saline there was a progressive decline in their ability to act as substrates for activation to an inhibitory product. It was possible to remove microsomes from the incubation mixture following drug activated by centrifugation. This microsome free mixture inhibited cell attachment. When MOT cells were added to the microsome free mixture attachment was inhibited.