In two investigations, we studied vulnerability to the negative effects of stress among women in chronic pain from 2 types of musculoskeletal illnesses, fibromyalgia syndrome (FMS) and osteoarthritis (OA). In Study 1, there were 101 female participants 50 to 78 years old: 50 had FMS, 29 had OA knee pain and were scheduled for knee surgery, and 22 had OA but were not planning surgery. Cross-sectional analyses showed that the three groups were comparable on demographic variables, personality attributes, negative affect, active coping, and perceived social support. As expected, FMS and OA surgery women reported similar levels of bodily pain, and both groups scored higher than OA nonsurgery women. However, women with FMS reported poorer emotional and physical health, lower positive affect, a poorer quality social milieu, and more frequent use of avoidant coping with pain than did both groups of women with OA. Moreover, the perception and use of social support were closely tied to perceived social stress only among the FMS group. In Study 2, we experimentally manipulated negative mood and stress in 41 women 37 to 74 years old: 20 women had FMS, and 21 women had OA. Participantsfrom each group were randomly assigned to either a negative mood induction or a neutral mood (control) condition, and then all participants discussed a stressful interpersonal eventfor 30 min. Stress-related increases in pain were exacerbated by negative mood induction among women with FMS but not women with OA, and pain during stress was associated with decreases in positive affect in women with FMS but not women with OA. These findings suggest that among women with chronic pain, those with FMS may be particularly vulnerable to the negative effects of social stress. They have fewer positive affective resources, use less effective pain-coping strategies, and have more constrained social networks than their counterparts with OA, particularly those who experience similar levels ofpain. They also seem to experience more prolonged stress-related increases in pain under certain circumstances, all of which may contribute to a lowering of positive affect and increased stress reactivity over time.