Depression is a major complication of cancer. The efficacy and safety of mianserin were evaluated in a randomized placebo-controlled trial of 73 depressed women with cancer. According to RDC diagnosis, all patients showed situational major depression. Both groups were well matched for cancer localization, clinical stages, Karnofsky scores, duration of depression, baseline values on the Hamilton Depression Rating Scale (HDRS), Zung Self-Rating Depression Scale (ZSRDS), and Clinical Global Impression of Illness Severity (CGI-S), and for type of depression, whether dominantly depressive or depressive-anxious. Between days 7-21, there were significantly fewer dropouts with mianserin (7) than with placebo (15). When compared with placebo, there were significant improvements for mianserin for HDRS on days 7, 21 and 28, for ZSRDS on days 7 and 28, and for CGI-S on days 7, 14, 21 and 28. According to Clinical Global Impression of Illness Improvement (CGI-I) there were significantly more responders with mianserin (28) than with placebo (18). The efficacy index for mianserin was significantly greater than for placebo on days 21 and 28. At the end of the trial the scores for HDRS sleep disturbance factor and HDRS anxiety-somatization factor were significantly reduced for mianserin than for placebo. There were no significant differences in side-effects between treatment groups. It is concluded that mianserin is superior to placebo in reducing the severity and duration of depression which is present especially in patients with advanced cancer.(ABSTRACT TRUNCATED AT 250 WORDS)