In the process of assisting pain patients' emotional and lifestyle problems, we noted men who after taking opioid medication became emotionally, verbally and physically defensive in ways indicative of low testosterone. As the assessments were based on clinical judgment, we investigated the relationship of opioids to low testosterone, hostility and anger. Chronic pain patients (CPPs) on at least 15 mg/day of methadone therapy for more than three months (G-2) were compared to CPPs on no opioids (G-1). All were ages 18-55 with 20-30 kg/m2 BMI. Exclusion criteria were history of orchidectomy, testosterone replacement, liver or kidney dysfunction, and alcohol use > twice weekly. SF-36 Health Survey measured physical and social functioning, mental and general health; MAACL-R measured anxiety, depression, and hostility; and STAXI-2 to gauged anger. We measured plasma levels of TT, FT, DHT, LH, FSH, E and PRO. ADAM measured sexual functioning. G-2 were significantly more anxious (p < .03) and dysphoric (P < .03), with less positive affect (p < .04) than G-1. There were no significant differences in expression of anger and hostility, trait hostility or anger. Both CPP groups had higher mean scores for depression, anxiety and hostility, and showed less positive affect, than the reference group of primary care patients. G-2 described more interference with social activities (P < .001) and less vitality (P < .005) than the control group, although both G-1 and G-2 fell considerably below the age-controlled group in the MAACL-R manual. Results demonstrate increased anxiety, depression/dysphoria and decreased sensation seeking for CPPs using methadone. On all anger scales there was a trend to suggest that we further investigate the effects of methadone or other opioids on the feelings, attitudes and behaviors of anger. We are now studying patients on other opioids to see whether all opioids affect mood and anger.