Prior research indicates that ACP hope to receive significant therapeutic benefit from phase I trial participation even in the face of advanced disease and presumed significant symptom burdens (SB). Yet, little is known about ACP SB and even less about ACP spousal caregivers' expectations of benefit. A convenience sample of ACP enrolling in phase I trials were evaluated at time of enrollment/baseline (T1) and one month later (T2) using an assessment designed to assess several components of symptom burdens including: MMSE; CES-D; STAI; PTGI; FACT-Pal; SF-36; and DAS. Quantitative interview data re: expectations of benefit from both ACP and spouses were obtained utilizing Likert scores (1–10) measuring the likelihood of chemotherapy in: "stabilizing" cancer; "halting/shrinking" cancer; producing "remission"; and "curing" cancer. Spouses were separately interviewed at T1 and T2. The data were analyzed by regression analyses. The hypotheses predicted that participants with greater SB would report lower expectations of benefit for trial, and that one's SB was associated with the other partner's expectations. For both groups, state anxiety was a significant predictor of ACP's and partners' expectation of trial benefit for stabilizing, halting, or producing remission for their cancer. As well, for the partners, associations were found between ACP's SB and partners' perceived SB at both T1 and T2. SB did not change over the course of the trial. Regression analyses revealed a negative association between ACP PTGI and spousal expectation of benefit scores for halting/shrinking the cancer at T1. At T2, negative associations were found between spousal expectation of benefit for halting/shrinking the cancer and domains/summary measures of QOL from the SF-36 as reported by the ACP including: General Health; Physical Functioning; Vitality; Role- Emotional; Mental Health; Physical Health; and Total SF-36 score. In addition, the following QOL-patient domains/summary measures were negatively associated with expectations of benefit as measured by spousal Likert scores for expectations re: stabilizing cancer at T2: General health; Role-emotional; Vitality; Physical Health; Mental Health; total SF-36 score. Using psychosocial measures, ACP SB are associated with spousal expectations of benefit in the phase I trial setting.