Corticosteroids have been used for many years for inflammatory diseases. Mood changes are common during short-term, high-dose, corticosteroid therapy. Virtually no data are available on the mood effects of long-term corticosteroid therapy. To evaluate mood during corticosteroid therapy using standard clinician-rated and patient-rated measures. Outpatients receiving prednisone therapy (7.5 mg/d for 6 months) and similar controls were enrolled. Current mood was evaluated using the Hamilton Rating Scale for Depression (HRSD), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS), Internal State Scale (ISS), and a diagnostic interview. Twenty patients and 14 controls were enrolled in the study. Depressive symptom severity as evaluated by the HRSD and ISS depression and well-being subscales and global psychiatric symptom severity as evaluated by the BPRS and ISS perceived conflict subscale were greater in patients receiving prednisone than controls. Manic symptom severity as evaluated by the ISS activation subscale but not the YMRS was higher in patients receiving prednisone. Twelve (60%) of 20 corticosteroid-treated patients met diagnostic criteria for a lifetime prednisone-induced mood disorder. Activation subscale scores did not correlate with YMRS scores. Other ISS subscales showed expected correlations with clinician-rated assessments. Mood symptoms and disorders are common in corticosteroid-dependent patients. Unlike short-term prednisone therapy, long-term therapy may be more associated with depressive than manic symptoms based on the clinician-rated assessments. The ISS may be more sensitive to mood symptoms with prednisone than clinician-rated scales.