We have confirmed the work of others showing that loss in body weight is a predictable and consistent sign of opiate withdrawal in rats. Rats that were treated chronically with either oxotremorine or physostigmine displayed no weight loss or other signs of opiate-like withdrawal when the drugs were withdrawn. Furthermore, there was no difference in weight loss between morphine dependent rats substituted with saline and those substituted with either cholinergic drug. However, we did observe an increased mortality among rats substituted with a cholinergic agent compared with saline. Rats infused with a mixture of morphine plus oxotremorine or morphine plus physostigmine showed less weight loss, but not fewer behavioral signs, after the end of the infusion than rats treated only with morphine. It is concluded that the cholinergic agents did not cause a morphine-like physical dependence themselves, but appeared to antagonize to some extent the development or manifestation of opiate dependence.