A cytogenic study of 16 opiate addicts receiving methadone hydrochloride compared with a control population revealed an unusual number of chromosome aberrations including dicentric chromosomes and an exchange figure at 72 hours in the addicted group, but no significant increase in chromosome anomalies over the controls at 48 hours. To determine whether methadone was the drug responsible for these chromosome abnormalities an in vitro study was initiated to evaluate the effects of methadone, morphine, and quinine on peripheral blood leukocytes from nonaddicts. Chromosome studies at three times normal, normal, and one third, one sixth, and one twelfth the normal therapeutic concentrations of quinine, morphine, and methadone introduced at 24, 48, and 68 hours into 72-hour leukocyte cultures did not reveal an increased frequency of chromosome damage.