This study examined the association between two primary covariates, extent of disease (ED) and performance status rating (PSR), and the outcome of psychological distress in patients with small cell carcinoma of the lung. Patients were studied at the time of entry onto one of three Cancer and Leukemia Group B (CALGB) protocols: 7781 (N = 165) and 8083 (N = 139) for limited disease; and 7782 (N = 151) for extensive disease. Besides ED (limited versus extensive), a four-point rating of PSR was obtained. Psychological distress was measured by the standardized Profile of Mood States (POMS). Gender, age, marital status, education, PSR, ED and two relevant interaction terms (PSR X ED; gender X ED) were analyzed using multiple linear and hierarchical regressions. Of the six main variables, gender and PSR had significant association with POMS total mood disturbance, a summary score for POMS emotional subscales, and most of the individual subscales. The PSR X ED interaction provided a rationale for testing a new regression model in which PSR and ED were combined into a single index of impairment. The final index resulted in five levels of physical impairment which bear an approximately linear relationship to increasing levels of distress (Overall regression, P < 0.001). These data suggest that PSR is an important factor in modelling POMS distress at both levels of ED, and that ED becomes an important factor with poorer performance status only.