['Patients on clinical trials often experience declining quality of life (QOL). Little is known about the psychosocial variables that buffer against decline.', 'This study aims to examine correlations between psychosocial variables and QOL over the course of a clinical trial in patients with metastatic renal cell cancer.', 'At baseline, 114 participants completed measures of treatment-related optimism, social support, and QOL (Functional Assessment of Cancer Therapy-General). QOL was also assessed 2, 4, and 8\xa0weeks after the start of treatment with low-dose or intermediate-dose interferon.', 'QOL decreased significantly in the intermediate-dose group but not in the low-dose group (p\u2009<\u2009.01). The decline was less severe for patients who had high rather than low treatment optimism (p\u2009=\u2009.03). A higher level of social support was significantly associated with higher baseline QOL (p\u2009<\u2009.05) but a more rapid decline in QOL over time (p\u2009<\u2009.01).'] Does treatment-related optimism protect quality of life in a phase II clinical trial for metastatic renal cell carcinoma?